The patient, a 52-year-old baker, had received the diagnosis of diabetes mellitus 5 years before his presentation to the neurologist and had been taking insulin for 2 years, with regular blood-sugar checks, under his family physician’s supervision. Despite good drug compliance and strict adherence to a low-sugar diet, he had had repeated episodes of hyperglycemia.
He presented complaining of burning pain in the toes of both feet, of 1 year’s duration, which had become progressively worse and then nearly intolerable. The neurologist found markedly diminished vibration sense in both feet and absent Achilles reflexes bilaterally. The patient could not spread his toes; when he dorsiflexed them, there was no palpable contraction of the muscles on the dorsum of the foot. The rest of the neurologic examination was normal.
The first step in neurologic diagnosis is always to pinpoint the site of the lesion in the nervous system with the aid of the detailed history and the neurologic examination. The findings generally reveal where the lesion is, as different parts of the nervous system serve different functions, and a loss of function in any particular part calls forth a characteristic collection of neurologic deficits, that is, a characteristic syndrome, as will be discussed in detail in this chapter.
This patient’s lesion must be situated in the peripheral nervous system, as can be seen from a combination of findings: the absent Achilles reflexes signify an interruption of the peripheral reflex arc, that is, damage to either its afferent (sensory) or its efferent (motor) component. The marked deficit of vibration sense and the spontaneous dysesthesia are evidence of an impairment of afferent fibers from the feet. The patient’s inability to spread his toes indicates weakness of the interosseous muscles of the feet, supplied by the tibial nerve on each side; weakness of the dorsal pedal muscles implies dysfunction of the motor fibers of the fibular nerve. All these findings taken together indicate a more or less symmetric impairment of motor and sensory fibers in multiple peripheral nerves—in particular, the longest nerves of the human body, those supplying the feet. This type of disturbance is called polyneuropathy. The cause here is diabetes mellitus, which impairs nerve function both directly (by hypoglycemia itself) and indirectly by way of diabetic microangiopathy and nerve ischemia. The longest nerve fibers are the most vulnerable ones to this type of disturbance, and thus diabetic polyneuropathy tends to begin in the feet.
The diagnosis of diabetic polyneuropathy motivated an attempt to optimize this patient’s glycemic control. To treat the pain, he was initially given lipoic acid for a few weeks, with indifferent results. A switch to carbamazepine led at first to transient and mild side effects, and thereafter to highly satisfactory, albeit subtotal, pain relief.
The clinical manifestations of neurologic disease are determined above all by the site of the lesion. Thus, the first step in neurologic diagnosis is always the localization of the disease process in the nervous system. This can usually be done very precisely on the basis of the patient’s symptoms and the findings of the neurologic examination. The etiology is sought in a second (or parallel) step with the aid of further information: the course of the disease over time, any accompanying nonneurologic manifestations, and ancillary test results.
In this chapter, we will show how the clinical manifestations of neurologic disease can be used to make inferences about the site of the lesion and its possible etiologies. We will first describe the typical findings of lesions affecting individual functional systems (the motor and somatosensory systems) and then those of lesions in particular areas of the brain. The manifestations of diseases affecting the spinal cord and peripheral nerves will be discussed later on in the relevant chapters.
5.2 Muscle Weakness and Other Motor Disturbances
Weakness can result from a disturbance at the level of the first motor neuron (cerebral cortex and pyramidal tract) or of the second motor neuron (anterior horn cells of the spinal cord, anterior root, peripheral nerve), or else from impaired conduction at the neuromuscular junction or from a disease of muscle. Disturbances of extrapyramidal structures cause complex movement disorders and abnormalities of muscle tone.
5.2.1 Anatomic Substrate of Motor Function
It is a useful simplification to consider the motor system as consisting of the first and second motor neurons, the neuromuscular junction, and the musculature ( ▶ Fig. 5.1).
Fig. 5.1 Anatomic substrate of movement.
First (Central) Motor Neuron The first motor neuron is located in the precentral gyrus. The axons travel in the corticobulbar and corticospinal tracts through the internal capsule and cerebral peduncle and terminate either in the cranial nerve nuclei of the pons and medulla (corticobulbar tract) or on the anterior horn cells of the spinal cord (pyramidal tract). Lesions of the first motor neuron in the precentral gyrus, or at any other site, produce the following deficits:
Spastic weakness (elevated muscle tone, diminished raw strength, and impaired fine motor control).
Increased intrinsic muscle reflexes, spreading of reflex zones, and pathologic reflexes (Babinski, Oppenheim, and Gordon reflexes, pathologically brisk Hoffmann sign, and Trömner reflex, inextinguishable or asymmetrically persistent clonus).
Diminished or absent extrinsic muscle reflexes (e.g., abdominal skin reflex).
No muscle atrophy (though there may be mild atrophy of disuse in the later course of disease).
Reflex asymmetry if the lesion is unilateral.
Second (Peripheral) Motor Neuron The second motor neuron originates in one of the motor relay stations mentioned earlier (the motor cranial nerve nuclei or the anterior horn cells of the spinal cord). It consists of a cell body (ganglion cell) and an axon that travels by way of a spinal nerve root, plexus, and peripheral nerve to the skeletal muscle. Each ganglion cell, together with its axon and the muscle fibers that it innervates (there may be many or only a few), comprises a single motor unit. The following deficits are associated with a lesion of the second motor neuron:
Flaccid weakness (diminished muscle tone and raw strength).
Diminished or absent intrinsic muscle reflexes.
Muscle atrophy becoming evident about 3 weeks after injury and progressing thereafter.
Motor End Plate and Muscle Normal motor function requires effective impulse transmission from the peripheral nerve to the muscle fiber, followed by fiber contraction. A lesion or functional disturbance of either or both of these elements causes flaccid weakness, usually accompanied by atrophy and diminished reflexes (see ▶ Table 15.1).
Coordination of Anatomic Structures Because every movement, as we have seen, is the product of a complex interaction of many different anatomic structures, motor processes are subject to a wide range of pathologic disturbances.
Typical findings of lesions of individual components of the motor system are listed in ▶ Table 5.1.
Some typical constellations of motor deficits, the likely site(s) of the lesion producing each, and some of the possible etiologies are listed in ▶ Table 5.2. This table reflects the classic threefold paradigm of clinical inference, from the findings to the site of the lesion to the diagnosis.
Table 5.1 Aspects of motor function and their localizing significance
Motor neuron in anterior horn
Spinal nerve root or peripheral nerve
Central motor pathway (corticobulbar and corticospinal)
Possibly rigid, possibly ↑
Ø (except for possible atrophy of disuse)
Intrinsic muscle reflexes
↓ or absent
↓ or absent
Extrinsic muscle reflexes
↓ or absent
↓ or absent
Pyramidal tract signs
Normal or ↓
Distribution of weakness
Corresponding to the affected root or nerve
Hemi-, para-, or quadriparesis, depending on site of lesion
5.2.2 Motor Regulatory Systems
The smooth, precise, and economic execution of a movement requires a properly functioning regulatory system, in addition to the effector components discussed earlier. The regulatory system must do the following:
Integrate proprioceptive input from the peripheral nerves, posterior columns (fasciculus gracilis and fasciculus cuneatus), thalamus, and thalamocortical pathways, along with further input from the vestibular apparatus and the visual system, and use these “feedback” data to optimize each phase of the movement at every moment.
Plan the force and amplitude of the movement (extrapyramidal system and cerebellum).
Coordinate the activity of all of the muscles taking part in the movement and, in particular, ensure the effective complementary functioning of agonist and antagonist muscles (extrapyramidal system, cerebellum, and spinal cord).
Loss of function of one or more components of this regulatory system impairs the execution and coordination of movement. Such disturbances typically manifest themselves as ataxia, hypokinesia, and involuntary movements.
Ataxia is an impairment of the smooth performance of goal-directed movement, with repeated deviation from the ideal line of a movement. The different types of ataxia have specific clinical features, depending on the nature and location of the underlying lesion.
Cerebellar Ataxia This form of ataxia is characterized by irregularity of the entire course of a movement. A lesion in a cerebellar hemisphere produces ataxia in the ipsilateral limbs, while a vermian lesion mainly produces truncal ataxia (ataxia of stance and/or gait; see ▶ Fig. 3.2). On the other hand, involvement of the dentate nucleus or its efferent fibers causes intention tremor: in targeted movements, such as pointing movements, the deviation from the ideal line of approach increases as the limb nears the target (see ▶ Fig. 3.22).
Central sensory ataxia This form of ataxia reflects impaired position sense due to lesions of the somatosensory cortex, the thalamus, or the thalamocortical pathways to the parietal lobe.
Posterior column ataxia (spinal ataxia) Spinal ataxia is produced by lesions of the afferent somatosensory pathways in the dorsal portion of the spinal cord (fasciculus gracilis and fasciculus cuneatus—also known as the columns of Goll and Burdach). It is most apparent when the patient walks; it is regularly accompanied by impaired proprioception and position sense. Patients can compensate for posterior column ataxia to some extent with visual cues; the ataxia is thus appreciably worse in the dark, or when the patient’s eyes are closed, than in a well-lit room with the patient’s eyes open.