and Gunhild Waldemar1
Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
The first step in the management of the neurological patient is to localize the lesion. While taking the history, the neurologist generates an anatomical hypothesis, which subsequently can be confirmed or rejected during the bedside examination. Following this, a working diagnosis is established and ancillary tests are chosen accordingly. Although the anatomy of the nervous system is highly complex, distinct anatomical entities have characteristic features. For instance, the hallmark of a myopathy is symmetric proximal weakness without sensory disturbances. Fatigability together with proximal weakness, including bulbar and oculomotor features, is typical for a disorder of the neuromuscular junction. In contrast, diseases of peripheral nerves, the brachial and lumbosacral plexus, as well as nerve roots usually lead to both motor and sensory deficits. Further, injury to the spinal cord is associated with a triad of paraparesis, a sensory level of the trunk, and sphincter disturbances. Brainstem processes often produce ipsilateral cranial nerve deficits and contralateral sensorimotor signs. While damage of the cerebellar hemispheres causes ataxia and intention tremor of the ipsilateral extremity, lesions of the midline region mainly lead to gait ataxia and truncal instability. Movement disorders due to disease involving the basal ganglia can be divided into hypo- and hyperkinetic disorders. Lesions involving the subcortical white matter frequently induce visual field deficits, complete hemiplegia, and dense numbness. Impairment of higher cognitive function, incomplete hemiparesis (sparing the leg), and epileptic seizures are common signs of cortical disease. This chapter reviews the relevant neuroanatomy from a clinical viewpoint and provides the reader with the tools to perform a competent clinical history.
KeywordsBasal gangliaBrachial plexusLumbosacral plexusBrainstemCerebellumCortexCranial nervesMuscleNerve rootsNeuromuscular synapsePeripheral nervesSpinal cordSubcortical white matterThalamus
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The neurological history differs from the history in other medical specialties insofar as it is primarily anatomy based. When examining a new patient, the first question a neurologist attempts to answer is, “Where is the lesion?” The main principle is to use the history to generate an anatomical hypothesis and to use the bedside examination to confirm this hypothesis. Following this, other features of the history, such as epidemiological data and the speed of symptom development, are taken into account in order to answer the next question, “What is the lesion?” Thereafter, the neurologist forms a differential diagnosis and a working diagnosis and then accordingly orders the most relevant laboratory tests. Strictly adhering to this schema allows for a safe and rapid diagnostic procedure. Obviously, in many cases, the experienced neurologist uses a shortcut called instant pattern recognition to reach a diagnosis. Yet, when confronted with a difficult diagnostic problem, nothing is more useful than to return to the bedside and take a more detailed history. Also, the history is more likely to lead to the correct diagnosis than the physical examination. Therefore, as a rule, more time should be devoted to the history compared to the bedside examination.
In order to obtain a neurological history, it is helpful to divide the complexity of the nervous system’s anatomy into small manageable entities (Fig. 2.1). From peripheral to central, these include:
Brachial and lumbosacral plexus
Cranial nerves (CNs)
Subcortical gray matter such as the thalamus and basal ganglia
Subcortical white matter
The nervous system’s anatomy can be divided into small manageable entities. Each anatomical unit has a specific symptomatology that can be elicited during the history
The subcortical white matter and the cortex can be further differentiated into:
Many diseases can be classified according to which of these entities they affect. For instance, myasthenia gravis (MG) is a disease of the neuromuscular synapse, while Alzheimer’s diesease (AD) and epilepsy are mainly disorders of cortical function. Importantly, each anatomical unit has a specific symptomatology that can be elicited during the history. The neurologist can therefore “examine” the patient from the muscle to the cortex solely by performing a good neurological history. The essential anatomical and clinical features are summarized in the following pages and in Table 2.1.
Summary of key anatomic features for history taking and bedside examination
Muscle: Proximal, symmetric weakness; no sensory symptoms
Neuromuscular junction: Fatigability; proximal, symmetric (or asymmetric) weakness; no sensory symptoms
Peripheral nerve: Sensory symptoms; distal, asymmetric weakness (except for symmetric polyneuropathy); normal or decreased muscle tone; hyporeflexia; eventually atrophy and fasciculations; motor and sensory deficits correlate to peripheral nerve distribution; sympathetic function (sweating) may be disturbed
Brachial plexus, lumbosacral plexus: Sensory symptoms; often distal greater than proximal weakness; normal or decreased muscle tone; hyporeflexia; eventually fasciculations and atrophy; motor and sensory deficits are neither consistent with a single peripheral nerve distribution nor with a specific dermatome/myotome; sympathetic function (sweating) may be disturbed; radiculopathic pain is common
Nerve root: Sensory symptoms; distal greater than proximal weakness; normal or decreased muscle tone; hyporeflexia; possibly atrophy and occasionally fasciculations; motor and sensory deficits associated with specific dermatome/myotome; radiculopathic pain; sympathetic function normal
Complete or near–complete transection or myelitis: Triad of paraparesis (spastic below site of lesion), sensory level, and sphincter disturbances
Anterior cord syndrome: Dissociated sensory loss with preserved vibration and proprioception but impaired perception of pain and temperature; paraparesis
Dorsal cord syndrome: Impairment of vibration and proprioception
Brown–Séquard syndrome (=hemitransection): Ipsilateral paresis; ipsilateral loss of vibration and proprioception; contralateral loss of pain and temperature
Syringomyelia (most often enlargement of cervicothoracic central cord): Dissociated sensory loss with bilateral impaired perception of pain and temperature; later bilateral paresis due to injury to nucleus of second motor neuron
Brainstem and cranial nerves: The brainstem includes (a) mesencephalon, (b) pons, and (c) medulla oblongata and consists of (x) all long afferent and efferent tracts, (y) vegetative centers (e.g., respiration), and the ARAS (arousal) and (z) nuclei of CN III–XII (mesencephalon III–V, pons V–VIII, medulla oblongata V and IX–XII). Thus, brainstem reflexes can be used to locate the lesion on a vertical axis (e.g., pupillary reflex, in, CN II, out, III; corneal and eyelash reflexes, in, V, out, VII; vestibulo-cephalic reflex and VOR, in, VIII, out, III and VI; and gag reflex, in, IX, out, X). Lesions often lead to ipsilateral CN and contralateral long tract signs, e.g., ipsilateral, peripheral (!) facial palsy, and contralateral hemiparesis. (However, if lesions affect the site above the nucleus of the facial nerve, there may be a contralateral, central facial palsy.) Other typical brainstem symptoms are, e.g., dysphagia, diplopia, and dysarthria (but not dysphasia, which is a cortical phenomenon)
Cerebellum: Cerebellar hemispheric lesions lead to ipsilateral (!) cerebellar ataxia and intention tremor. Cerebellar midline lesions lead to gait and truncal ataxia (without severe ataxia of the extremities)
Subcortical gray matter: Consists of basal ganglia, thalamus, and hypothalamus; deficit of dopamine functions leads to parkinsonism (tremor, bradykinesia, rigidity, postural instability) and dopamine hyperfunction to, e.g., chorea
Subcortical white matter: Visual field deficits, dense numbness, complete hemiparesis, executive dysfunction, and decreased psychomotor speed
Cortex: Impairment of higher cognitive function, including amnesia, aphasia, apraxia, visuospatial deficits, and neglect; epileptic seizures; incomplete hemiparesis sparing the leg; frontal lobe (executive dysfunction, personality impairment, hemiparesis due to lesions of the supplemental motor area and primary motor cortex, nonfluent or motor dysphasia); temporal lobe (auditory hallucinations due to lesions of the primary auditory cortex, memory disturbance with damage to the hippocampal formation, rising epigastric sensation and automatisms with temporal lobe seizures, fluent or sensory dysphasia); parietal lobe (visuospatial disorientation, sensory hemisymptoms due to lesions of the sensory cortex); and occipital lobe (visual hallucinations and cortical blindness with damage to primary visual cortex)
Although it is of preeminent importance not to push the patient into reporting the symptoms that one is trying to elicit, the history must be meticulous and detailed. A useful clinical rule is that after finishing the history, one should have a clear and detailed idea of what has happened and be able to fully visualize the sequence of events. The focus should be on the principal symptoms and signs; the neurologist should not let minor findings and uncertain clinical data distract from the greater picture. (Admittedly, this is not easy without experience.) If the patient has many different and seemingly unrelated complaints, it is useful to ask what bothers him most and then concentrate on this complaint.
Taking a history is difficult in patients with a disorder that affects the level of consciousness, communication skills, and/or cognitive function, e.g., due to amnesia, aphasia, impaired judgment, lack of insight, and confabulation. A patient with AD, for instance, may not be able to explain his symptoms or the course of the disease; if he can, it might well be that not all of the information can be taken at face value. Likewise, the aphasic patient following a left middle cerebral artery (MCA) occlusion may have difficulties understanding the examiner’s questions, or he may well understand but be unable to formulate an appropriate answer. Further, a patient with a frontal brain tumor may have become so apathetic and indifferent that he might not complain at all despite an obvious inability to perform basic activities of daily living. In contrast, a patient with locked-in syndrome due to a large pontine infarct following a basilar artery thrombosis is awake and may fully understand the examiner but has lost all efferent motor control except for a few eye movements. Similarly, patients with terminal amyotrophic lateral sclerosis (ALS) or fulminant Guillain-Barré syndrome (GBS) may be anarthric and unable to communicate verbally. In all these situations, prior to taking a formal history, it is the duty of the neurologist to evaluate the cognitive capabilities of the patient and to find appropriate means of communication, e.g., by establishing a reliable code for locked-in patients to indicate yes and no using blinking or vertical eye movements. Also, it is of utmost importance to ensure that all other sources, e.g., spouses, family, friends, nurses, ambulance personnel, and patient notes, are taken into account to establish a history that is as detailed and as accurate as possible.
The hallmark of a generalized myopathy is proximal symmetric weakness without sensory symptoms. For assessment of proximal weakness of the lower extremities, ask the patient about difficulties rising from a chair, getting out of bed, climbing stairs, or leaving the car without using his arms to pull himself up. In order to rise from a sitting position, a patient with severe weakness of the hips and thighs may have to flex his trunk at the hips, put his hands on his knees, and push his trunk upward by working his hands up his thighs. To discover upper extremity weakness, ask about problems working with the arms above the shoulder girdle. For instance, the patient may be unable to lift a child or a heavy bag, hang laundry on a clothesline, or wash his hair in the shower. Note that delicate hand movements usually do not present any difficulties, which is why writing, turning a key in the keyhole, or manipulating small buttons are not problematic. A patient with severe myopathy has a characteristic stance and gait pattern with marked lumbar lordosis. Also, when standing, the patient places his feet wide apart to increase the base of support, while his gait is characterized by the pelvis tilting from side to side because of bilateral weakness of the gluteus medius muscles. Thus, the patient “straddles as he stands and waddles as he walks.”1
Importantly, the neurologist needs to rule out sensory symptoms. A myopathy may be painful, but a clear complaint of sensory symptoms is not compatible with a myopathic syndrome.
Hereditary myopathies may lead to involvement of cardiac muscle as well; thus, it is mandatory to ask for signs of cardiomyopathy and cardiac arrhythmias.
Other signs of muscle disease include:
Scapular winging, e.g., limb–girdle muscular dystrophy and facioscapulohumeral muscular dystrophy (FSH).
Orofacial weakness, e.g., FSH and myotonic dystrophy.
Ptosis, e.g., mitochondrial disease, oculopharyngeal muscular dystrophy, and myotonic dystrophy.
Gowers’ sign. In order to rise from the ground, children with, e.g., Duchenne muscular dystrophy (DMD), may have to assume a four-point position by fully extending the arms and legs and then working each hand alternately up the corresponding thigh.
Muscle hypertrophy, e.g., the athletic appearance in myotonia congenita.
Pseudohypertrophy of muscles, e.g., enlargement of the calves due to replacement of muscle cells by fat tissue as seen in DMD.
Muscle contractures. Boys with DMD, for instance, may have to walk on their toes because of contractures of the gastrocnemius muscles.
Distal weakness, e.g., hand weakness in myotonic dystrophy, weakness and atrophy of finger flexors and wrist flexors in inclusion body myositis (IBM), and weakness of the thumbs and index fingers in late–adult type 1 distal myopathy (Welander or the Swedish type of distal myopathies).
Myotonia. A patient with myotonic dystrophy may complain of difficulties releasing his hand after a handshake. Patients with myotonia congenita exhibit very stiff, awkward movements after resting. Movements become smoother after a few minutes, the so-called warm-up phenomenon.
Pseudomyotonia. This is seen in paramyotonia congenita of von Eulenburg. In contrast to myotonia, pseudomyotonia becomes worse with exercise. Typically, cold temperatures increase symptoms, e.g., patients may complain about delayed eye opening and facial rigidity in the winter.
Local atrophy, e.g., temporalis muscle atrophy in myotonic dystrophy; atrophy of finger flexors, wrist flexors, and quadriceps muscles in IBM; and limb-girdle atrophy in limb-girdle muscular dystrophy and FSH.
Progressive external ophthalmoplegia is encountered in mitochondrial disorders. Extramuscular manifestations of mitochondrial disorders include diabetes, hearing loss, a short stature, and dysfunction of the heart, kidneys, and liver.
Exercise intolerance with or without subsequent rhabdomyolysis and myoglobinuria is seen in glycogen storage disorders such as McArdle disease and lipid storage disorders such as CPT II deficiency (“Has your gym teacher in school been angry with you because he thought you were lazy?” “Does your urine look like cola after you have been exercising?”). Characteristically, in lipid storage myopathy, myalgia occurs after exercise. In glycogen storage disorders, in contrast, myalgia tends to occur during exercise. After a few minutes of prolonged exercise, patients may experience a characteristic “second wind,” and the pain may disappear due to metabolic adaptation of the muscles to enhance fat oxidation.
Periodic weakness induced by hypo- or hyperkalemia, e.g., severe generalized but transitory weakness in potassium–related channelopathies.
Skeletal deformities such as high palate, elongated facial appearance, pes cavus, chest deformities, and hip luxations are seen with congenital myopathies, e.g., nemaline myopathy, central core disease, and centronuclear myopathy. Patients with congenital myopathies usually present as “floppy babies” after birth, but the deficits often stabilize in later life, leading to relatively mild functional impairment. A history of severe myopathic weakness during childhood, improving and stabilizing during adolescence, and nasal speech because of a high palate are the main clues to the diagnosis of a congenital myopathy.
Respiratory muscle weakness, e.g., Pompe’s disease, leading to dyspnea, but also to more unusual presentations such as confusion or headache because of hypercapnia.
It is important to remember, however, that despite the large amount of space reserved in neurological textbooks for rare muscle diseases, the commonly encountered myopathies in general clinical practice are drug–induced myopathies (e.g., steroids, statins) and inflammatory myopathies (e.g., polymyositis, dermatomyositis). These are all characterized by the signs mentioned at the beginning of this chapter: proximal, symmetric weakness without sensory symptoms.
2.2 Neuromuscular Junction
Similar to myopathies, a disorder of the neuromuscular junction is characterized by proximal weakness without sensory symptoms. However, the hallmark of neuromuscular junction disorders such as MG is muscular fatigability. The symptoms therefore are of a waxing and waning nature. Symptoms may be better in the morning and worse in the evening; for instance, diplopia commonly increases during the afternoon. Yet it is generally of little use to ask about greater fatigability in the evening—who would say no? Instead, what needs to be elicited in the history is the following sequence: During a specific muscular activity, weakness develops. After a while weakness becomes so severe that the patient is forced to take a break, after which muscular strength normalizes. The activity is taken up again with normal or near-normal power, but after a while decreasing strength makes another break necessary, and so on. Examples include patients with masticatory weakness who cannot eat a whole meal without having to stop several times and patients whose speech becomes progressively dysarthric during a conversation, forcing them to pause often to regain their voice.
Weakness in most neuromuscular junction disorders is so proximal that it affects nuchal, facial, pharyngeal, and external ocular muscles. Consequently, head drop,2 decreased facial expression, dysphagia, dysarthria, and ophthalmoplegia may develop. The smile of a myasthenic patient is highly characteristic. The face can be completely motionless except for half-raised corners of the mouth (it has been suggested that Leonardo’s Mona Lisa has a myasthenic facial expression). Facial weakness may send highly negative social signals to someone not familiar with the disease. Symptoms in MG are often somewhat more asymmetric than in a myopathy; e.g., ptosis and ophthalmoplegia can be much worse on one side than the other. Dyspnea is seen with affection of the respiratory muscles and acute respiratory failure is the most dreaded complication. MG tends to affect young women or elderly men. In the latter, outcome is sometimes still rather poor.
A history of bulbar symptoms arising in several individuals from the same household or who have shared a meal is highly suggestive of botulism (see Case 2.1 and Chap. 4). Lambert–Eaton myasthenic syndrome (LEMS), in contrast, seldom leads to bulbar symptoms. The usual presentation of LEMS is with generalized proximal upper and lower limb weakness and signs of autonomic dysregulation such as a dry mouth. Therefore, LEMS patients often carry a bottle of water with them. If these symptoms occur in a smoker, a diagnosis of small cell lung cancer is highly likely.
Botulism. A 16-year-old male developed diarrhea 2 days after ingestion of spoiled canned tofu, followed the next day by double vision, impaired swallowing, and weakness in the arms and legs. Neurological examination revealed external ophthalmoplegia, bilateral facial palsy, (a, b; the patient tries to smile) anarthria, proximal tetraparesis, and absent tendon reflexes (c). Of note, loss of pupillary reflexes was seen not earlier than on the fifth day of admission. The patient was fully awake and communication was possible by sign language (thumbs up, thumbs down). The initial differential diagnosis included botulism and GBS. A lumbar puncture revealed normal protein and cell count. Analysis for anti-GQ1b antibodies, suggestive of Miller-Fisher syndrome, was negative. Electromyography and nerve conduction studies, including repetitive nerve stimulation and single fiber studies, were reported twice as normal but later revealed a neuromuscular transmission defect. Following a positive mouse bioassay test for botulism toxin, a diagnosis of botulism was made. One year later, the patient had made a full recovery (d)
2.3 Peripheral Nerves, the Plexus, and Spinal Nerve Roots
In contrast to muscle or neuromuscular junction disorders, weakness is usually combined with sensory symptoms in diseases of the peripheral nerves, the plexus, and the nerve roots (Fig. 2.2). In addition, symptoms tend to be more asymmetric (with the important exception of a symmetrical polyneuropathy) and more distal. Since the lower motor neuron (LMN) is affected, motor weakness is characterized by normal or decreased muscle tone, hyporeflexia, and eventually muscle atrophy and fasciculations.3
The characteristic features of a mononeuropathy include sensory and muscular symptoms attributable to an individual peripheral nerve (e.g., carpal tunnel syndrome with compression of the median nerve at the wrist).
The hallmark of a nerve root lesion is a combination of sensory and muscular symptoms derived from a specific dermatome and myotome (e.g., radiating pain in the L5 dermatome and weakness of dorsiflexion of the great toe in a L5 root disc herniation).
The hallmark of a plexus lesion is that it comprises sensory and muscular symptoms that do correspond neither to a dermatome nor a myotome nor to a lesion of a single nerve. Plexus lesions therefore tend to have a more complex symptomatology than peripheral nerve lesions. Also, plexus and peripheral nerve lesions may impair sympathetic function, such as sweating, in contrast to nerve root lesions.
Sensory innervation. Segmental distribution of the cutaneous nerves and typical dermatome distribution of the human body
While it is often difficult to differentiate between peripheral nerve, plexus, and root lesions by the history alone, there is a very characteristic feature of root lesions—and to a lesser extent of plexus lesions—that does not occur in peripheral nerve disorders. This feature is radiculopathic pain. A patient with radiculopathic pain usually has a history of chronic neck or lumbar pain acutely exacerbated by severe, electric shock-like pain that radiates down the arm or leg. Described differently, a sharp sudden pain, often evoked by abrupt cervical or lumbar movements, shoots from the neck and shoulders into the hands or from the lumbar spine into the feet. Pain from a peripheral lesion, in contrast, is more distal and localized. Carpal tunnel syndrome may lead to pain in the entire arm, but the pain clearly does not originate from the neck. Thus, the simple question “Do you feel sharp, sudden pain coming from your neck and radiating down your arm?” differentiates a C6/7 radiculopathy from carpal tunnel syndrome.
Some words of comfort: Although the anatomy of the peripheral nervous system (PNS) can be rather intimidating, the vast majority of clinically relevant features are due to lesions of only a few PNS structures. In the upper extremities, these include five nerve roots, the upper and the lower brachial plexus, and six peripheral nerves and in the lower extremities, three nerve roots and the cauda equina, the lumbosacral plexus, and eight peripheral nerves (Fig. 2.3). Knowing the signs and symptoms associated with lesions at these anatomical sites enables the categorization of the great majority of peripheral nerve disorders.4
Peripheral nervous system. Although the anatomy of the PNS is complicated, the great majority of patients will have symptoms and signs that can be attributed to lesions of only a few PNS structures
2.3.1 Peripheral Nerves
As mentioned above, peripheral nerve lesions generally cause a sensory deficit that may or may not be accompanied by a motor deficit. This distinguishes them from primary lesions of the muscle or of the neuromuscular junction, which never cause a sensory deficit. Also, symptoms in peripheral nerve disorders tend to be distal, and they are usually asymmetric (with the important exception of distal symmetric polyneuropathies). Since the lower motor neuron is affected, weakness is “flaccid”—thus, muscle tone is normal or decreased, and there is hyporeflexia and eventually atrophy and fasciculations. The motor and sensory deficits follow the distribution of the affected peripheral nerve.
Many peripheral nerve disorders have a typical history. Complaints involving walking on cushions, pins, and needles and burning sensations in the feet, particularly in a patient with alcoholism or diabetes mellitus, are typical of distal symmetric polyneuropathy. Only in severe cases are the hands affected, usually when hypesthesia and paresthesia in the lower extremities have reached half way up to the knees. (This represents the “length-dependent” pattern of axonal degeneration. Rarely, in especially severe cases of polyneuropathy, the truncal nerves can be affected as well—this leads to hypesthesia in the middle of the abdominal wall, where the most distal branches of the cutaneous nerves meet, an area that roughly corresponds to the rectus abdominis. In contrast to a sensory level associated with spinal cord lesions, sensation is intact in the back and the waist.) A painful neuropathy with prominent distal dysesthesias (burning feet syndrome) is seen with small fiber disease.5 A complaint about not being able to walk in the dark, in contrast, is characteristic for the sensory ataxia of large fiber disease.6 These patients cannot go to the bathroom at night without having to turn on the light. The gait unsteadiness is of the so-called stamp and stick type; the patients may need a walking aid and stamp their feet on the ground in order to activate all the remaining proprioceptive nerve fibers. Besides sensory ataxia, examination reveals a positive Romberg’s sign, hypo- or areflexia, distal weakness, and atrophy of the small muscles of the feet.
Symmetric polyneuropathy, distal wasting, pes cavus, clawed toes, and palpable peripheral nerves point toward hereditary polyneuropathy. This is usually due to Charcot–Marie–Tooth (CMT) disease or a related disorder but is also seen in a few other conditions, e.g., Friedreich’s ataxia.
The most common cause of acute neuromuscular weakness in the developed world is GBS. In Europe and North America, the most common variant of GBS is acute inflammatory demyelinating polyneuropathy (AIDP). AIDP is essentially a polyradiculoneuropathy (which is why high protein, leaking from inflamed nerve roots, is found in the cerebrospinal fluid (CSF)). Patients usually present with progressive ascending weakness with areflexia affecting the limbs more or less symmetrically. Symptoms are maximally expressed after 2 weeks in 50% of patients and after 4 weeks in 90%. Hyperacute onset with quadriplegia within 48 h or less is not uncommon, and in these patients reflexes may be initially preserved. Facial diplegia, respiratory failure, and autonomic dysfunction such as cardiac arrhythmias and labile blood pressure are frequent. Sensory symptoms and neuropathic pain are usual complaints but tend to be much less significant than motor paralysis. Red flags indicating that the diagnosis is wrong include persistent asymmetric weakness, early bladder and bowel paralysis, and a sensory level suggesting a spinal cord lesion. More than half of GBS patients have a history of gastrointestinal (GI) and upper respiratory tract infection or vaccination 1–3 weeks prior to symptom onset. GBS variants are numerous. Among the more important are pharyngeal-cervical-brachial paresis, oculopharyngeal weakness, pure sensory GBS, pure autonomic failure, ataxic GBS, and the Miller-Fisher syndrome. The last variant mentioned is associated with GQ1b antibodies and consists of the triad of ophthalmoplegia, ataxia, and areflexia, although oligosymptomatic and overlapping syndromes exist. In contrast to AIDP, paralysis in the Miller-Fisher syndrome is usually descending. Axonal variants (acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN)) represent only 3–5% of GBS cases in the Western world but are much more common in the Far East and South America. GBS mimics include diphtheric polyneuropathy (beware of a history of recent pharyngitis in patients without diphtheria vaccination) and porphyric polyneuropathy (classically associated with abdominal pain, psychosis, and dark urine). Nerve conduction studies reveal demyelinating features in the former and axonal features in the latter.
More or less symmetric ascending sensorimotor paralysis with hypo- or areflexia that develops during a period of 8 weeks or more is typical of chronic inflammatory demyelinating polyneuropathy (CIDP). Differentiation between GBS and CIDP is important for prognosis and treatment. While CIDP can be treated with steroids, GBS cannot. In contrast to GBS, multiple CN involvement, life-threatening dyspnea, and acute autonomic dysfunction are very rare with CIDP. The list of differential diagnoses for CIDP is long. Relapsing GBS, subacute GBS, alcoholism, nutritional deficiencies, paraneoplastic conditions, heavy metal poisoning, and certain drugs such as amiodarone, cisplatin, isoniazid, and nitrofurantoin may all give rise to a similar clinical picture that develops within a few weeks or months.
Monoclonal gammopathies (IgM, IgA, and IgG) are found in 10% of patients with idiopathic neuropathy. Polyneuropathy associated with a monoclonal gammopathy may be the presenting features of a plasma cell dyscrasia or may be related to a monoclonal gammopathy of unknown significance (MGUS). In addition, IgM-MGUS polyneuropathies can be associated with autoantibody activity against peripheral nerve glycoproteins such as myelin-associated glycoprotein (MAG). MGUS polyneuropathies typically affect patients over the age of 50, men roughly twice as often as women. A minority of patients with polyneuropathy associated with a monoclonal gammopathy have significant motor involvement and are clinically indistinguishable from those with CIDP, while in the majority of patients, the condition is chronic, mainly sensory and only slowly progressive, distal, and symmetric.
Mononeuritis multiplex is a form of asymmetric polyneuropathy in which several peripheral nerves are affected at the same time or subsequently. In full-blown mononeuritis multiplex, the patient complains of multiple motor and sensory symptoms in the extremities, which may often be rather painful. With time, mononeuritis multiplex may involve so many peripheral nerves that it simulates a peripheral polyneuropathy. The differential diagnosis includes metabolic (diabetes), immunologic (rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus (SLE), amyloidosis), infectious (HIV, leprosy, neuroborreliosis), malignant (leukemia, lymphoma), and vasculitic disorders (Churg-Strauss vasculitis, polyarteritis nodosa, Wegener granulomatosis). Vasculitic neuropathies also occur without systemic manifestations; characteristically, they often include the sciatic nerve.
Multifocal motor neuropathy (MMN) is a predominantly distal, mainly upper limb, asymmetrical pure motor neuropathy. The male–female ratio is 2.5:1. A typical patient would be a middle-aged man with progressive (asymmetric) weakness in his arms, but normal sensation and who is concerned about having amyotrophic lateral sclerosis (ALS). In contrast to ALS, profound muscle atrophy is usually absent. Severe bilateral arm palsy in either MMN or ALS with preserved power in the legs occasionally leads to the “man-in-the-barrel syndrome,” where the arms hang uselessly at the patient’s side as if his trunk were trapped in a barrel. Another characteristic clinical feature that may be observed in a patient with ALS is dissociated atrophy of intrinsic hand muscles, known as the ALS split hand. The split-hand phenomenon refers to preferential wasting of the thenar muscles with relative sparing of the hypothenar muscles. Although the exact mechanisms remain elusive, it is a highly specific diagnostic sign in early ALS (Case 2.2). The clinical presentation and differential diagnosis of ALS, a disorder affecting the lower as well as the upper motor neuron (UMN), are discussed in Chap. 4.
Split-hand sign in amyotrophic lateral sclerosis. A 73-year-old female was referred for progressive weakness, which had started 3 years earlier in her right hand. Subsequently, her right leg became involved, followed by her left extremities. Despite cervical and lumbar decompressive surgery, she had started using a walking stick and then a walking frame 2 years and 12 months, respectively, prior to admission. At the time of referral, she was confined to a wheel chair. Swallowing had become increasingly difficult during the previous 3 months. Examination revealed dysphagia, a pronounced jaw jerk, and marked atrophy and fasciculations in all four extremities. Cognition and sensory functions were intact. Of note, dissociated atrophy of intrinsic hand muscles was noted. The ALS split hand refers to preferential wasting of the thenar muscles (abductor pollicis brevis (a) and first dorsal interosseous muscles (b)), with relative preservation of the hypothenar muscles (lateral abductor digiti minimi muscles). Both cortical and peripheral mechanisms have been suggested, but the origin of the split-hand sign remains poorly understood. Nevertheless, it is a useful diagnostic sign in early ALS with a high degree of specificity
In hereditary neuropathy with liability to pressure palsies (HNPP), motor symptoms typically predominate over sensory symptoms. Patients often complain that after trivial compression of the extremities, the subsequent numbness and dysesthesia last from days to months rather than minutes. Also, there is a tendency that minor or moderate compression of peripheral nerves, such as may occur when carrying heavy weights during housework and other trivial activities, leads to episodes of focal palsies. Childbirth, for instance, can give rise to a palsy of the lumbosacral plexus. When weakness is secondary to limb compression during sleep, the weakness will typically be noticed when the patient wakes up in the morning. The attacks in HNPP are usually of sudden onset and painless. Typically affected nerves are those associated with a specific anatomic vulnerability, e.g., in the arms, the radial (humerus), median (carpal tunnel), and ulnar (cubital tunnel) nerves, and in the legs, the peroneal nerve (compression at the fibular neck). But HNPP may also affect more uncommon nerves; e.g., it may lead to recurrent, sometimes bilateral, peripheral facial palsies, usually after the patient has rested his face on a hard surface. Mononeuropathies are initially followed by recovery, although patients with repeated episodes may have lasting neurologic abnormalities. A less common manifestation of HNPP is that of a more or less symmetric, slowly progressive polyneuropathy. With this subtype, high arches and hammertoes are common, which may lead to a misdiagnosis of CMT disease. At symptom onset, HNPP patients are typically in their 20s or 30s but, occasionally, patients may become symptomatic earlier or later in life. HNPP is inherited in an autosomal dominant fashion, so there is often a positive family history, but spontaneous mutations are well described.7 Apart from entrapment neuropathy, electrophysiological examination typically shows a background demyelinating polyneuropathy, suggesting the correct diagnosis.
Sensory ganglionitis, also termed sensory neuronopathy, is due to inflammation of the sensory root ganglia. With the involvement of large-diameter ganglionic neurons, the main symptoms include a severe sensory ataxia of the arms and legs. With arms elevated and eyes closed, the patient may show typical pseudo-athetoid movements of the fingers. (This is simply because the patient does not know the exact position of the fingers.) With affection of small-diameter neurons, symmetric or asymmetric numbness, paresthesias, and burning pain occur and frequently involve the face or the trunk early in the development of sensory ganglionitis. (This is the so-called pseudo-syringomyelia distribution or the numb-chin syndrome, which is very characteristic for a sensory neuronopathy.) There are four major forms of noninfectious sensory ganglionitis:
Acute sensory neuronopathy syndrome (often postinfectious; young and old, women and men are equally affected; this is a sensory variant of GBS)
Subacute paraneoplastic sensory neuronopathy (e.g., occurring in middle-aged men with small cell lung cancer)
Subacute sensory neuronopathy associated with Sjögren syndrome (usually affecting middle-aged women)
Chronic ataxic neuropathy associated with paraproteinemia or polyclonal gammopathy with or without known autoantibodies (typically affecting the elderly, mostly men)
The most common infectious cause of sensory ganglionitis is herpes zoster due to reactivation of a dormant ganglionic varicella zoster virus (VZV), typically manifesting with an extremely painful rash in the affected dermatome.
Another sensory neuropathy is Wartenberg’s migrant sensory neuritis (WMSN), in which the site of the lesion is much more peripheral. WMSN is a harmless, rare disorder of unknown etiology. It involves multiple cutaneous nerves and has a highly characteristic history, which is the clue to the diagnosis. An ordinary movement of a limb (e.g., stretching in bed, turning a key, putting on socks) induces a sudden brief pain in the distribution of a cutaneous nerve followed by sensory loss in the distribution of this nerve. Sensory loss may persist for several weeks. A complaint of motor symptoms is not compatible with this disorder. Different cutaneous nerves are affected at different times. WMSN may thus have a relapsing-remitting character, which is why it is a useful differential diagnosis to multiple sclerosis (MS). (See Case 3.13 for illustration.)
Another condition that deserves to be mentioned is the syndrome of painful legs and moving toes (PLMT). Although it remains poorly understood, PLMT is an easily recognized and distinct clinical entity. Patients complain about severe burning pain in the legs and more or less constant involuntary movements of the toes (occasionally also of the fingers). The movements are suggestive of both chorea and dystonia. The most frequent etiologies are cryptogenic and peripheral neuropathies, followed by trauma and radiculopathies. PLMT responds poorly to treatment, and quality of life can be severely compromised because of debilitating pain.
220.127.116.11 Mononeuropathies of the Upper Extremities
The most common causes of mononeuropathies in the upper extremities are nerve entrapment and trauma.
In the upper extremities, a lesion of the axillary nerve (C5/C6) may lead to a weakness of shoulder abduction and sensory loss over the outer aspect of the upper arm.
Isolated lesions of the musculocutaneous nerve (C5/6) are usually secondary to a fracture of the humerus. They lead to wasting of the biceps brachii muscle, the brachialis, and coracobrachialis muscles and to weakness of flexion of the supinated forearm. Rupture of the biceps brachii muscle tendon may sometimes simulate wasting of the biceps brachii muscle, but differentiation between these two conditions is usually possible with careful inspection.
Rucksack palsy is compression of the long thoracic nerve (C5–7) leading to a posterior shoulder or scapular burning type of pain and scapular winging due to weakness of the serratus anterior muscle. This is seen with sports injuries or in soldiers and backpackers carrying heavy weights on their backs for a prolonged period, hence the name rucksack palsy. Paralysis of the long thoracic nerve and the serratus anterior muscle is the most frequent neuropathic cause of scapular winging, leading to medial winging of the scapula. Lateral winging, in contrast, is generated by trapezius and rhomboid muscle paralysis due to injury to the spinal accessory (CN XI) and dorsal scapular nerves (C4–6), respectively.
Paresis of the radial nerve (C5–8) is often encountered in patients who have consumed large amounts of alcohol and have slept with the back of their arms compressed by the back of a bench or a similar object. It is thus also known as Saturday night palsy and leads to a drop hand, an inability to actively extend the fingers, and numbness of the back of the hand and wrist. Another variety of this syndrome is called Honeymoon palsy, which occurs in a patient whose bed partner has slept on the affected arm. Radial nerve is also seen with humeral fracture. Although exceedingly rare in the developed world nowadays, a classic cause of bilateral hand drop due to radial motor neuropathy is lead poisoning.8
Compression of the ulnar nerve (C8/T1) provokes a tingling sensation in the little finger, half of the ring finger, and the ulnar half of the hand and is usually due to entrapment or trauma at the elbow in the cubital tunnel (colloquially called the funny bone). Importantly, ulnar nerve injury does not lead to sensory symptoms above the wrist. (Sensory disturbances above the wrist on the ulnar aspect of the forearm therefore suggest a lesion of the lower brachial plexus or of the C8/T1 nerve roots.) With long-standing nerve compression, a claw hand may develop. The fact that a distal lesion at the wrist, despite affecting fewer muscles, leads to more pronounced clawing than a proximal lesion is called the ulnar paradox.
Median nerve (C6–T1) entrapment as seen in carpal tunnel syndrome is the most common of all nerve entrapment syndromes. A typical patient may complain about pins and needles in the thumb, index, and ring finger and in the medial aspects of the palm, but in practice, the patient may state that the entire hand and even the arm are involved. The condition can be rather painful. Symptoms usually awaken the patient at night and disappear when the hand is shaken and massaged. Later, symptoms also occur during daytime; especially dorsiflexion of the hand, e.g., during bicycling, may aggravate the symptoms. With long-standing median nerve entrapment, atrophy of the thenar muscle develops and the thumb drops back in the plane of the other digits, which leads to the so-called ape hand. Lightly tapping over the nerve at the wrist may elicit a typical sensation of tingling or pins and needles in the distribution of the nerve (Tinel’s sign). The so-called reverse Phalen’s test is a provocative examination maneuver during which the patient is asked to maintain full wrist and finger extension for 2 min, thereby increasing pressure in the carpal tunnel. Paresthesias in the distribution of the median nerve make carpal tunnel syndrome diagnosis likely. A variety of conditions predisposes to carpal tunnel syndrome, e.g., pregnancy, trauma, rheumatoid arthritis, acromegaly, and hypothyroidism.
18.104.22.168 Mononeuropathies of the Lower Extremities
Meralgia paresthetica is due to compression of the lateral cutaneous nerve of the thigh (L2/3) beneath the inguinal ligament and affects men more often than women. The patient complains of numbness and burning pain over the anterolateral aspect of the thigh, but since the entrapped nerve is purely sensory, muscle power is normal. Examination reveals impaired or altered sensation in the same area, but there is no motor weakness or wasting and the knee jerk is preserved, distinguishing it from radiculopathy. Sometimes symptoms are caused by tight trousers, and a history of recent weight gain or weight loss is common. Obesity and pregnancy may be contributing factors, and certain habitual postures (e.g., sitting or prolonged standing for an obese person) may be particularly uncomfortable.
Injury to the femoral nerve (L2–4) leads to weakness of extension of the lower leg. In long-standing cases, there are wasting of the quadriceps muscle and failure of knee fixation. The patient may complain that the knee seems to give way and that climbing stairs is impossible. If the nerve is damaged proximal to the origin of the branches to the iliacus and psoas muscle, hip flexion is affected as well. In contrast to L3 radiculopathy, thigh adduction (mediated by the obturator nerve) is spared. A sensory deficit can be found on the anterior aspect of the thigh and the ventromedial aspect of the calf (supplied by the saphenous nerve). The most common cause of an isolated femoral neuropathy is diabetes mellitus. Femoral neuropathy is also seen with pelvic tumors, after surgery for hernia repair, appendectomies, hysterectomies, and similar operations in the pelvis. A hematoma in the iliopsoas muscle is a frequent cause of femoral neuropathy in patients with anticoagulation or hemophilia. These patients complain about acute pain in the groin and characteristically assume a posture of flexion and lateral rotation of the hip.
The obturator nerve (L2–4) may be damaged by the fetal head or forceps during prolonged delivery. Other common causes include pelvic tumors, fractures, and obturator hernia. Thigh adduction is affected and sensory loss is found on the medial aspect of the distal thigh.
Lesions of the superior (L4–S1) and inferior (L5–S2) gluteal nerves, seen with misplaced intragluteal injections, direct trauma, or injury during childbirth, evoke a characteristic gait disturbance. When walking, the patient typically bends his trunk away from the affected side in order to compensate for mild weakness of the hip abductors. This phenomenon is called the Duchenne limp. With severe abductor paresis, lateral bending of the trunk is insufficient to prevent pelvic tilt toward the normal side (Trendelenburg’s sign). If abductor paresis is bilateral, the patient has a typical waddling gait.
The sciatic nerve (L4–S3) is the largest peripheral nerve in the body. Prior to its division into the tibial and common peroneal nerve, the sciatic nerve supplies the skin and the muscles of the back of the thigh (e.g., the knee flexors). Its tibial and peroneal nerve branches innervate all the muscles below the knee as well as the skin of the foot and the outer and dorsal aspects of the lower leg. Sciatic nerve lesions thus provoke a variety of combinations of tibial and common peroneal nerve palsies. When the nerve is proximally injured, knee flexion may be impaired as well. Partial sciatic nerve lesions are more common than complete sciatic paralysis and tend to affect peroneal-innervated muscles more than tibial ones. Common causes of sciatic nerve damage include pelvic fracture, hip dislocation, misplaced injections into the lower gluteal regions, pressure from a toilet seat during a period of alcohol intoxication (“toilet seat palsy”), sitting in the lotus position (“yoga paralysis”), and lying flat on a hard surface for a prolonged time. The last cause mentioned is sometimes encountered in slender drug addicts or cachectic patients who are bedridden. Stab and gunshot wounds causing sciatic nerve lesions are fortunately rare.
The common peroneal nerve (L4–S2) emerges within the poplitea and turns around the fibular head—a common area of compression—where it divides into the superficial and the deep peroneal nerves. A lesion of the superficial branch affects the peroneus muscles and thereby elevation of the lateral edge of the foot (eversion). It also leads to sensory disturbances at the lateral aspect of the distal leg and the dorsum of the foot. Of note, elevation of the medial aspect of the foot (inversion) is spared, since this is mediated by the tibial nerve. Indeed, preserved inversion of the foot (together with preserved abduction of the hip) is the main clinical finding that distinguishes a peroneus lesion from a L5 radiculopathy. The deep peroneal nerve mediates dorsiflexion of the foot and toes and innervates the skin in a small zone between digits I and II. Peroneal nerve damage leads to a drop foot and the typical steppage gait. The patient must flex the hip and lift the knee in order that the foot, which cannot be dorsiflexed, can clear the ground. Peroneal nerve impairment may arise spontaneously or follow prolonged pressure at the fibular head due to, e.g., leg crossing, tight casts, activities in the kneeling position, and improper positioning during anesthesia. In patients with apparently spontaneous drop foot, a history of significant weight loss is not uncommon. Shrinkage of the subcutaneous fat tissue, usually protecting the nerve, is probably a causative factor. Common traumatic causes of foot drop include fracture of the fibular head (e.g., due to a skiing accident) and knee dislocation.
The tibial nerve (L4–S3) mediates inversion of the foot, flexion of the toes, and sensation of the sole of the foot. Isolated tibial nerve damage is uncommon because the tibial nerve is rather well protected in the poplitea. It may occur following hemorrhaging in the knee or after direct trauma, such as a knife stab. Baker cysts are a rare cause of peroneal or tibial nerve compression. Tarsal tunnel syndrome is due to compression of the tibial nerve beneath the flexor retinaculum in the tarsal tunnel. It leads to pain and pins and needles in the foot and sometimes the leg. Another condition that provokes pain in the foot, mostly in the forefoot, is metatarsalgia. It may be primarily a problem of the joints and bones of the metatarsals, or it may be due to a neurinoma of the plantar nerve branches (Morton’s neuroma). Muscle power is preserved in tarsal tunnel syndrome and metatarsalgia.
The pudendal nerves (S2–4) innervate the external genitalia as well as the sphincter of the anus and bladder. Stretching of the nerves during prolonged childbirth can result in incontinence and perianal sensory disturbances. The latter is also sometimes encountered in bicyclists after prolonged rides on hard saddles. Dysfunction of the nerve is usually temporary in the latter conditions, whereas with pelvic surgery or a tumor, the pudendal nerves may be damaged permanently.
2.3.2 Brachial Plexus and Lumbosacral Plexus
As with peripheral nerve and nerve root lesions, motor weakness due to a plexus lesion is typically accompanied by sensory deficits, and symptoms are unilateral. Since it is the second motor neuron that is affected, there may be normal or decreased muscle tone, hyporeflexia, fasciculations, and atrophy. The hallmark of a plexus lesion is that motor and sensory deficits follow neither the distribution of a single peripheral nerve nor a specific dermatome/myotome. The patient with a lesion of the plexus may complain of strong pain in the shoulder or hip with or without radiation into the extremities. In contrast to a lesion of the nerve root, plexus pathology may impair sympathetic function. This is because the fibers from the sympathetic trunk join the sensory and motor fibers distally to the nerve roots. As a consequence, decreased sweating within a localized area may be seen with a plexus or peripheral nerve lesion, but not with nerve root compression.
Plexus lesions are rather rare; this is especially true for lesions of the lumbosacral plexus, which is well protected. The three most serious disorders resulting in painful plexopathies are due to trauma, malignancy, and radiation injury. The most common painful plexopathy, which has an excellent prognosis, is brachial neuritis.
For all practical purposes, lesions of the brachial plexus (C5–T1) can be divided into upper and lower plexus syndromes. A lesion of the upper brachial plexus (C5–C7), or Erb palsy, can be encountered in infants after traumatic delivery. Upper brachial plexus palsies acquired in adult life are usually due to trauma, e.g., because of a motorcycle accident. They result in the loss of the lateral rotators of the shoulder, arm flexors, and hand extensor muscles. Thus, the patient’s arm hangs by his side and is rotated inward, and the dorsum of the slightly flexed hand faces forward, which is known as the characteristic waiter’s tip position.
A lesion of the lower brachial plexus (C8–T1) is sometimes called Klumpke paralysis. Sudden upward pulling of the elevated arm stretches the lower brachial plexus. Symptoms include paralysis of intrinsic hand muscles, which may lead to a claw hand and hypesthesia in the ulnar aspect of the forearm. Involvement of sympathetic fibers from the T1 nerve roots results in ptosis, miosis, and anhidrosis (Horner’s syndrome). Again, frequent causes in adults are motorcycle accidents and, in infants, complicated deliveries. However, malignancy is frequent as well, e.g., a smoker with shoulder pain, numbness in the lower arm, and ulnar weakness, and a unilateral Horner’s syndrome most likely has a tumor of the lung apex, termed Pancoast tumor (Case 2.3).
Pancoast tumor. A 45-year-old female smoker complained of right-sided shoulder pain and numbness in the forearm that had lasted for 2 months. Examination revealed weakness of the ulnar muscles of the right hand and an ipsilateral Horner syndrome (a). The chest X-ray showed a right-sided tumor of the lung apex (b). Biopsy confirmed the diagnosis of a small cell carcinoma of the lung
Plexus neuritis (also called Parsonage-Turner syndrome, neuralgic amyotrophy, or brachial neuritis) manifests with severe sudden-onset shoulder pain, often awakening the patient during the night. Weakness, atrophy, and fasciculations typically develop when the pain subsides after some hours or days. (Occasionally, weakness may also manifest right from the beginning.) Often the condition affects muscles served by the upper brachial plexus, and elevating the arm above the shoulder may become impossible. However, all arm and shoulder muscles may be affected in isolation or in combination. A similar condition has been suggested as an explanation for sudden unilateral diaphragm weakness due to an isolated palsy of the ipsilateral phrenic nerve. The prognosis of plexus neuritis is usually good. In most cases weakness resolves after a few months. Presumably of autoimmune origin and often occurring after an upper respiratory infection, the disorder has also been described after delivery, surgical operations, trauma, and many other conditions. In addition, there is an autosomal dominant form of recurrent plexus neuritis called hereditary neuralgic amyotrophy.
Lumbar and sciatic pains are some of the most frequently encountered syndromes in general practice and are usually caused by degenerative spinal disease affecting lumbosacral nerve roots, such as discopathy or stenosis of the intervertebral foramen. However, when local signs of spinal disease are absent in spite of leg weakness, sensory loss, and reflex asymmetry, when sweating is disturbed, or when the patient has a history of negative radiological examination of the spine, peripheral plexopathy becomes more likely. In adults lumbosacral plexus (L1–S4) pathology is probably more often than not due to a malignancy. Primary or metastatic visceral and extravisceral tumors lead the list, but mass lesions due to Hodgkin’s disease and other lymphoreticular and hematogenic disorders are also seen. Benign causes include, among others, diabetic plexopathy, radiation plexopathy, and spontaneous or iatrogenic retroperitoneal hemorrhage. Since the lumbosacral plexus lies deeply in the retroperitoneal space, trauma must be severe to affect the plexus and therefore almost always leads to pelvic fracture as well.
2.3.3 Spinal Nerve Roots
The ventral and dorsal spinal nerve roots form 31 pairs of spinal nerves (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal). Lesions of nerve roots, usually due to disc herniation and degenerative spine disease, occasionally due to neuroma or schwannoma, typically provoke radiculopathic pain and sensory and motor symptoms. Weakness tends to be more pronounced distally than proximally. Muscle tone may be normal or slightly decreased. Physical examination reveals hyporeflexia or areflexia. Fasciculations are usually not a significant finding. The hallmark of a nerve root lesion is that the motor and sensory deficits are confined to a specific dermatome and myotome (Fig. 2.4).
Normal spinal cord anatomy. (a) Central canal, (b) ventral horn, (c) lower motor neuron nucleus, (d) corticospinal tract, (e) lower motor neuron axon, (f) ventral nerve root, (g) dorsal column, (h) sensory ganglion, (i) sensory dendrite (dorsal nerve root), (k) sensory axon, (l) spinal nerve, (m) intervertebral foramen, (n) posterior column, (o) synapse between first and second sensory neuron, (p) commissura alba (contralateral spinothalamic pathway not shown), (q) spinothalamic tract. Black, motor pathway; dark blue, spinothalamic pathway; light blue, posterior column pathway
Degenerative spine disease typically affects the spine where it is most mobile. Thus, lower lumbar (L4–S1) and lower cervical (C5–C8) nerve roots are most frequently damaged. Lesions of other nerve roots are rare. Most disc herniations affect the lower nerve root, e.g., a lateral L4/L5 disc protrusion typically leads to compression of the L5 nerve root, and a medial L4/L5 disc protrusion may compress the L5 nerve root and also sacral nerve roots. In contrast, a far lateral disc herniation may occasionally affect the upper nerve root, e.g., a very laterally protruded L5/S1 disc may lead to compression of the L5 nerve root.
Lumbosacral disc herniation, which is the classic cause for sciatica, is more common than cervical disc herniation. A patient with lumbar nerve root compression typically complains about chronic lumbar pain exacerbated by sudden radiculopathic pain radiating down into the foot. Heavy weight lifting or other strenuous exercise preceding symptom onset for a few hours or days may or may not be reported. Coughing, defecation, and other forms of Valsalva maneuver typically increase the pain. However, it should be noted that degenerative spine disease as revealed by magnetic resonance imaging (MRI), for instance, is very common and often asymptomatic.
With damage to the L5 nerve root, examination may reveal a positive Lasègue’s sign, a drop foot, paralysis of ankle dorsiflexion, and—in contrast to what is seen with a “simple” peroneal nerve lesion—impaired inversion of the foot and abduction of the thigh. With long-standing L5 nerve root damage, atrophy of the small dorsal foot muscles may occur.
With S1 nerve root compression, sensory disturbances occur in the lateral aspect of the leg and the foot. Plantar flexion may be impaired and the Achilles reflex will be diminished.
L3/4 disc herniation with L4 nerve root compression is somewhat less common and manifests with sensory disturbances on the anterior aspect of the thigh and the medial aspect of the leg, weakness of knee extension, and a diminished patellar reflex.
Cauda equina syndrome is due to damage to the lumbar and sacral nerve roots along their path within the spinal canal prior to their exit through the intervertebral foramina. The syndrome is often combined with conus medullaris syndrome, which will be discussed later in this chapter. Involvement of sacral nerve roots (S1–S4) leads to saddle anesthesia and sensory disturbances in the lateral aspect of the legs and the feet, bowel and bladder sphincter disturbances with urinary retention, and fecal incontinence, as well as erectile dysfunction in males. If the lumbar roots are involved as well, there is paraparesis of the LMN type. Pain may or may not be present. A cauda equina syndrome may have traumatic, degenerative (e.g., spinal lumbar canal stenosis, median disc herniation, ankylosing spondylitis), vascular (e.g., epidural hematoma), metastatic (e.g., meningeal carcinomatosis, lymphoma), inflammatory, and infectious causes. A common infectious agent is herpes simplex virus (HSV) II, affecting the spinal nerve roots retrogradely. Women are at higher risk than men. The patient complains of sudden onset of urinary retention with or without saddle anesthesia. Power in the legs is usually normal. The patient is not necessarily aware of being infected with HSV II; indeed, cauda equina syndrome may manifest without visible genital herpes. Tactful questioning often reveals that the patient has a new sexual partner.
Analogous to lumbar spine disease, cervical spine pathology usually presents with chronic neck pain exacerbated with radiculopathic pain and paresthesias. Injury to the C5 nerve root leads to disturbed sensory function on the outer aspect of the shoulder and over the deltoid muscle. Abduction of the shoulder is impaired and the biceps reflex diminished.
C6 nerve root compression provokes radiating pain in the thumb and index finger and the radial aspect of the forearm. The biceps reflex will be lost or decreased, and there is weakness of arm flexion at the elbow.
Damage to the C7 nerve root impairs arm extension, affects the triceps reflex, and leads to pain and numbness in the second, third, and fourth finger and the dorsal aspect of the forearm.
Compression of the C8 nerve root also impairs arm extension at the elbow and diminishes the triceps reflex, but sensory symptoms will typically be confined to the fourth and fifth finger and the ulnar aspect of the forearm.
2.4 Spinal Cord
Spinal cord anatomy is rather complex (Fig. 2.4). Damage to the spinal cord therefore leads to many different but highly specific symptom constellations. The following is a simplified and selective review of spinal cord anatomy that nevertheless provides all that is needed to understand the clinical syndromes associated with spinal cord lesions.
On a transversal section, the gray matter of the spinal cord has a butterfly appearance and is surrounded by white matter (Fig. 2.4). In the middle of the butterfly is the central canal (a) that communicates with the brain’s ventricles. The hind wings of the butterfly correspond to the right and left ventral horns (b) in which the nuclei of the LMNs (c) reside. The axons from the UMNs are termed the corticospinal tract.9 The corticospinal tract (d) descends in the lateral aspect of the spinal cord. The axons of the UMNs synapse with the LMNs in the ventral horn. The axons of the LMNs (e) leave the gray matter and form the ventral nerve root (f).
The forewings of the butterfly form the right and left dorsal horns (g) that receive sensory information. However, the cell body of the peripheral sensory neuron is located in the dorsal spinal root ganglion (h). This nerve cell, the first sensory neuron in a chain of three, is a pseudounipolar cell. This means that it has one very short axon that, still within the spinal ganglion, divides into a distal process (actually the dendrite (i)) that conveys sensory information from the periphery (skin, muscle, internal organs) and a proximal process (essentially, this is the axon (j)) that reaches the spinal cord via the dorsal nerve root. Distal to the sensory dorsal root ganglion, the dorsal root and the ventral root merge into the spinal nerve (k) that leaves the spine through the intervertebral foramen (l).
For all practical purposes, sensory information can be divided into sensation mediated by:
Posterior column pathways (vibration, proprioception, and light touch)
Spinothalamic tracts (pain, temperature, and crude touch)
The posterior column pathway (or, more correctly, the posterior column-medial lemniscus pathway) mediates vibration, proprioception, and fine touch. Upon entering the spinal cord via the dorsal nerve root, fibers that convey vibration and proprioception travel upward through the ipsilateral posterior column (m).10 The spinothalamic pathway that conveys temperature, pain, and crude touch, in contrast, crosses over to the contralateral side at the same level the fibers enter the spinal cord (or one or two segments higher). The axons from the first sensory neuron (of the spinothalamic pathway) synapse with second sensory neurons in the ipsilateral dorsal horn (n). Then, the axons of the second-order neurons cross the midline just anterior to the central canal. Together with the contralateral pain and temperature fibers, they form a white cross of myelinated nerve fibers within the gray matter. This white cross can be seen under the microscope and is called the commissura alba (o). Having crossed the midline, the fibers ascend in the anterior-lateral aspect of the spinal cord; this is the spinothalamic tract (p).11
The spinothalamic pathway mediates pain and temperature and decussates at the level of the spinal cord. This pathway ascends in the white matter region that lies anterior and laterally to the butterfly.
The posterior column-medial lemniscus pathway conveys vibration and proprioception. It ascends ipsilateral to the entry of the dorsal root and crosses the midline at the brainstem level.
The corticospinal tract decussates also at the brainstem level and descends laterally to the butterfly and synapses with the peripheral motor neuron in the frontal horn.
Sympathetic fibers leave the thoracolumbar spinal cord (T1–L2) via different routes compared to sensory and motor fibers. They also join the spinal nerves distally via the sympathetic trunk. This is why nerve root compression does not impair sweating, in contrast to what may be seen with a lesion of the plexus or a peripheral nerve.
Note that the anatomical site of a spinal cord lesion may differ from the clinical level found during bedside examination. This is due to certain features of the spinal vascular supply and the topography of the motor and sensory pathways. There are cases of paraparetic patients operated on for an asymptomatic cervical spinal stenosis who later were found to suffer from thoracic meningioma. Complete neuroimaging of the spinal cord helps avoid such mistakes.
2.4.1 Complete or Near-Complete Transection of the Spinal Cord
Complete or near-complete transection of the spinal cord (Fig. 2.5), as seen with trauma, tumor, hemorrhage, vascular malformations, and infectious and autoimmune myelitis (e.g., neuromyelitis optica (NMO)), leads to the pathognomonic triad:
Paraparesis (or tetraparesis)
Sensory disturbances below a “sensory level” on the trunk
Spinal cord transection. Traumatic and nontraumatic spinal cord transections lead to a classical triad of paraparesis, a sensory level on the trunk and sphincter disturbances (black, motor pathway; dark blue, spinothalamic pathway; light blue, posterior column pathway
It is of utmost importance to identify this triad in both the history and bedside examination in every patient suspected of harboring a spinal cord lesion (Case 2.4). Transection of the spinal cord at the cervical level leads to tetraparesis and, if the C3–C5 level is involved, diaphragm palsy and acute dyspnea (“C three, four, and five keep the diaphragm alive.”). Levels below T1 lead to paraparesis only. During the first phase of severe spinal injury following the traumatic event (“spinal shock”), muscle tone is lost, the weakness is flaccid, and there is hypo- or areflexia. (Note, however, that with incomplete spinal cord injury, hyperreflexia may be found immediately after the injury.) When the spinal shock resolves after days or weeks, weakness usually becomes spastic below the lesion because the corticospinal tract is disrupted. Thus, UMN signs including increased muscle tone, spasticity, hyperreflexia, and extensor plantar reflexes develop. There is one important exception to this rule. At the very level of the spinal cord lesion, the ventral horn and thus the cell bodies of the LMNs are also damaged. Therefore, LMN signs such as flaccid weakness, decreased reflexes, atrophy, and fasciculations may develop at precisely this level. However, the clinical level of the spinal cord damage resulting in motor weakness is best established by assessing the presence or absence of weakness in key muscles. In the upper extremities, these include:
C5 elbow flexion
C6 wrist extension
C7 elbow extension
C8 long finger flexion
T1 finger abduction
Compressive cervical medullopathy in Down syndrome. A 49-year-old male with Down syndrome and associated Alzheimer’s disease fell off the swing while playing on a playground. He was unable to get up from the ground as his legs gave way. The neurologist on call noticed hyperreflexia in all extremities, bilateral extensive toes, and urinary retention. The patient was unable to participate in a detailed sensory examination, but sensation for pain and temperature seemed decreased below the clavicles. Emergency MRI showed a cervical compressive medullopathy. The patient underwent emergency spinal surgery. Compression of the cervical spinal cord due to atlantoaxial instability (or, as in this case, slightly below this level) is a well-known complication of trisomy 21 (as is progressive cognitive decline due to early onset Alzheimer pathology), which is caused by the triplication of the amyloid precursor protein gene (APP located on chromosome 21)
And in the lower extremities:
L2 hip flexion
L3 knee extension
L4 ankle dorsiflexion
L5 great toe extension
S1 ankle plantar flexion
With acute para- or tetraparesis, symptoms will usually be so obvious that a detailed history of motor function is not necessary. However, with subacute or slower development, the most common complaints are stiffness of the legs, decreased walking distance, and dragging of one or both feet.
The patient is usually aware of a clear sensory level, but in cases where sensory disturbances are less pronounced, he may only report a band-like sensation on the trunk. The site of the sensory level corresponds to the uppermost dermatome that is functionally affected by the injury. This usually (but not always) reflects the site of the anatomical lesion. A sensory level corresponds to:
T4 dermatome if involving the breast nipples
T10 dermatome if involving the umbilicus
L1 dermatome if involving the inguinal ligaments
As with muscles of the extremities, the sphincters tend to be paralyzed during the phase of spinal shock. In mild spinal cord injuries, bladder sphincter disturbance is usually more pronounced than anal sphincter dysfunction, resulting in urinary retention. Later, bladder sphincter and detrusor muscles become spastic and urinary urgency may develop. Voluntary anal contraction must always be assessed in the patient with acute spinal cord injury, and its presence or absence should be documented in the charts. With severe spinal cord injuries, temporary paralysis of the GI tract usually occurs. Sexual dysfunction, including erectile dysfunction, is another frequent symptom; all patients with spinal cord injury need empathetic guidance and help with their sexuality.
With chronic spinal cord injury above TH6, painful stimuli in the body below the transection level may lead to acute massive vasoconstriction of the mesenterical vessels and arterial hypertension. This is due to massive uninhibited sympathetic discharge. Characteristically, the patient is “cold and pale” below the lesion and “red and hot” above. This is called autonomic dysreflexia and represents a true medical emergency. Since patients with chronic injury to the cervical or upper thoracic spinal cord usually have very low blood pressure, even blood pressure readings with apparently normal values (e.g., 130/80 mmHg) may be associated with life-threatening hypertensive encephalopathy. Chapter 6 discusses the treatment of autonomic dysreflexia.
2.4.2 Brown-Séquard Syndrome
Hemitransection of the spinal cord is called Brown-Séquard syndrome and denotes a lesion affecting the right or left half of the spinal cord (Fig. 2.6). Classical hemitransection is usually only encountered after knife stabs or gunshots, but less complete hemitransection may be seen with, e.g., an epidural tumor or hemorrhage and lateral cord compression.
Motor function will be lost below and ipsilateral to the lesion; thus, a right-sided truncal hemitransection leads to paresis of the right leg. Again, below the lesion weakness is usually spastic, whereas at the level of the lesion, there will be LMN palsy.
Since the ipsilateral dorsal column is affected, vibration and position sense are impaired in the ipsilateral leg.
Pain and temperature sense will be affected in the contralateral side of the trunk and the leg due to damage of the spinothalamic tract crossing at the spinal level.
Brown-Séquard syndrome (spinal cord hemitransection). Spinal cord hemitransection is associated with injury to the ipsilateral motor pathway (black), the ipsilateral posterior column pathway (light blue), and the contralateral spinothalamic pathway (dark blue)
Rephrased, examination of the ipsilateral leg will reveal motor paresis and decreased sensation for vibration and position sense but normal pain and temperature sensation: the contralateral leg, in contrast, will have intact motor function and normal sensation for vibration and proprioception but disturbed sensation for pain and temperature. This is termed dissociated sensory loss. (Thus, spinothalamic tract sensation is affected, but dorsal column sensation is intact—and vice versa.) Dissociated sensory loss is a highly characteristic sign of spinal cord pathology.
2.4.3 Anterior Cord Syndrome
Infarction of the anterior spinal artery is usually due to occlusion of the artery of Adamkiewicz or of one or several of the many smaller feeding arteries and may occur spontaneously or secondary to, e.g., aortic dissection and thoracic surgery. It leads to the anterior cord syndrome (Fig. 2.7). Since the spinal anterior artery supplies the ventral two-thirds of the spinal cord, there is dissociated sensory loss with preserved vibration sense and proprioception but impaired perception of pain and temperature below the affected level. In addition, the patient has a paraparesis with LMN signs at the level of the lesion and upper motor signs below it.
Anterior cord syndrome. With damage to the anterior spinal cord, usually due to infarction of the anterior spinal artery, the ventral two-thirds of the spinal cord will be damaged, leaving the vibration sense and proprioception intact (black, motor pathway; dark blue, spinothalamic pathway; light blue, posterior column pathway)
Compressive cervical myelopathy may occasionally affect the anterior horns selectively and lead to bibrachial diplegia of the LMN type. This is another differential diagnosis of the man-in-the-barrel syndrome. Mechanical compression of the spinal cord can be temporary and may be overlooked with MRI in neutral position, e.g., cervical flexion myelopathy associated with an intradural cyst. Spinal cord compression during neck flexion is also well described in Hirayama disease (juvenile muscular atrophy of the distal upper extremity), a self-limiting, distal, brachial mono- or diplegia due to segmental anterior horn cell lesion, typically affecting young people, frequently of Asian origin. Sensory symptoms do not occur. The hallmark of this disease is anterior displacement of the cervical spinal cord against the vertebral bodies during neck flexion, visualized only on MRI in flexed position.
2.4.4 Dorsal Cord Syndrome
Dorsal cord syndrome (Fig. 2.8) is characterized by impairment of vibration and proprioception in the legs. Sensation of pain and temperature and motor function are preserved. The most characteristic sign of this syndrome is sensory ataxia. The patient may complain of being unable to walk in the dark or to stand with eyes closed (Romberg’s sign). A manifestation of neurosyphilis, tabes dorsalis is a classic example of tertiary syphilis. It is exceedingly rare in the developed world nowadays, although syphilis itself is on the rise again. Subacute combined degeneration due to vitamin B12 deficiency and copper deficiency myelopathy have a predilection for the dorsal columns as well but also affect the corticospinal tracts, thus leading to a combination of decreased sensation for vibration and position sense and spastic leg weakness. Another example of dorsal cord dysfunction is the useless hand of Oppenheim, occasionally encountered with MS. Whereas power and cutaneous sensation are preserved, loss of proprioception induced by a plaque in the dorsal columns makes the hand more or less useless.
Dorsal cord syndrome. Posterior column function is impaired, but spinothalamic and motor pathways usually stay intact (black, motor pathway; dark blue, spinothalamic pathway; light blue, posterior column pathway) (Color figure online)
Syringomyelia indicates the presence of a fluid-filled cavity (syrinx) within the spinal cord (Fig. 2.9). This cavity can expand and elongate over time, damaging the spinal cord. Syringomyelia in its classic presentation is due to enlargement of the central canal of the cervical and thoracic cord, also termed hydromyelia. Extracanalicular syrinxes, in contrast, are associated with, e.g., cystic spinal tumors or may be seen following absorption of a spinal hemorrhage. The pathophysiology is not well understood. Syringomyelia may arise spontaneously and is often an incidental finding on MRI of the spine. Secondary causes include spinal trauma, hemorrhage, tumor, and myelitis. Syringomyelia is also frequently encountered in patients with congenital hydrocephalus and the Arnold-Chiari syndrome. Symptomatic syringomyelia has a typical clinical presentation. For unknown reasons, when the central canal dilates, it affects the ventral horn first. The first structures to be damaged are the myelinated fibers of the spinothalamic pathways that cross immediately ventral to the central canal. This is the commissura alba referred to earlier (Fig. 2.4). Since syringomyelia normally affects the cervicothoracic spine, patients present with loss of pain and temperature perception in the hands. They often have a history of painless wounds and injuries to the hands. Only later does the syrinx involve the whole of the ventral horns and then LMN signs develop, including atrophy, fasciculations, and deformities of both the hands and arms. Continuing enlargement of the syrinx may then damage the ventral horns of the thoracic spinal cord and lead to weakness and atrophy of the truncal musculature and to scoliosis. Bulbar signs such as dysarthria, dysphagia, and tongue paresis can occur with extension of the syrinx into the medulla oblongata. This condition is called syringobulbia.
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