Abscess, Brain


Respiratory acidosis, respiratory alkalosis, metabolic acidosis, metabolic alkalosis

Brain abscess is a focal pyogenic infection of the brain parenchyma. They constitute less than 2% of intracranial masses and develop mainly in four clinical situations, although 15% to 20% are cryptogenic.

  1. I. Contiguous spread (45%–50% of all cases) via direct extension from local neighboring infection sites—frontal or ethmoid sinusitis or dental infection (frontal lobe abscess), middle ear or mastoid air cell infection (temporal lobe and cerebellar abscess), spread by local osteomyelitis or by septic thrombophlebitis of emissary vein.
  2. II. Hematogenous spread from distant sites of infection (25%), usually multiple and multiloculated, often in the middle cerebral artery distribution. Common sources of metastatic brain abscesses are pulmonary or abdominopelvic infections, cyanotic heart disease, congenital heart malformations with right-to-left shunts (oral bacterial flora after dental procedures), or bacterial endocarditis.
  3. III. Trauma including penetrating head injury or neurosurgical procedures (10%)—compound depressed skull fractures, basal skull fractures with cerebrospinal fluid (CSF) fistulae/leak, and previous craniotomy can lead to brain abscess, sometimes months or years after the acute event. Postneurosurgic abscesses may occur, especially when surgery involves paranasal air sinuses.
  4. IV. Immunosuppression. People with acquired immune deficiency syndrome (AIDS) or with other causes of immunosuppression (e.g., neoplasms, steroid use) are susceptible to bacterial infections or infections associated with decreased T-cell immunity such as mycobacteria, fungi, or Toxoplasmosis.

Pathogens isolated from abscesses are related to the site of origin, as follows (organisms are listed in order of significance; many abscesses are polymicrobial):

  1. I. Middle ear infection: streptococci (aerobic and anaerobic), Bacteroides fragilis, and Enterobacteriaceae (Proteus).
  2. II. Sinusitis: same as middle ear infections, plus Staphylococcus aureus, Haemophilus species, and mucormycosis (also seen with orbital cellulitis).
  3. III. Penetrating head trauma: S. aureus, streptococci, Enterobacteriaceae, Clostridium species, and Pseudomonas aeruginosa.
  4. IV. AIDS/immunocompromised: Toxoplasma, Mycobacterium, Listeria species infection, Listeria monocytogenes, Nocardia, and Cryptococcus neoformans.

Clinical features

Clinical features usually resemble those of other space-occupying lesions (focal signs, seizures in 25%–35% of patients) with most symptoms related to increased intracranial pressure (ICP) (headache, nausea, vomiting, lethargy, and stupor). Fever occurs in only 50% of cases.

Histopathologic stages


  1. I. Blood cultures should be drawn (positive in 15% of cases) and empiric parenteral antibiotic therapy must be initiated before computed tomography (CT) scan or magnetic resonance imaging (MRI). Lumbar puncture may be considered if mass effect is not prominent. However, the diagnostic yield is low and the risk of herniation is greater with abscess than with other mass lesions.
  2. II. CT scans correlate well with the histopathologic stages. In the cerebritis stage, CT without contrast shows the necrotic center as a hypodensity. Ring enhancement begins in the later stages of cerebritis. In capsular stages the capsule becomes visible on CT without contrast as a faint hyperdense ring that produces ring-enhancing lesion with contrast, which is thinner on the ventricular side.
  3. III. MRI appearance is bright on diffusion-weighted images (DWIs): T1 delineates the abscess capsule as hyperintense/isointense and hypointense center and surrounding edema; T2 demonstrates the hyperintense edema and center and hypointense capsule, enhances with gadolinium.
  4. IV. MR spectroscopy (MRS) can differentiate between abscess, necrotizing tumor, or granuloma. The main finding of MRS in abscesses is elevation of metabolites of bacterial origin, including acetate, lactate, succinate, and amino acids versus necrotic brain tumors with elevated choline and decreased N-acetylaspartate (NAA). The MRS pattern may monitor effectiveness of medical treatment of a brain abscess, showing a decline of the metabolites after a positive response to therapy.
  5. V. Other studies include electroencephalogram (EEG) which may show nonspecific findings such as focal slowing, seizure activity, and evidence of encephalopathy. Cerebral angiography may show avascular mass and luxury perfusion.


A combination of broad-spectrum antimicrobials, management of raised ICP, neurosurgical drainage or excision, and eradication of the primary infectious focus is indicated. If CT shows only cerebritis or abscess less than 2.5 cm and the patient is neurologically stable, antibiotics without surgery may suffice. Neurologic deterioration usually mandates surgery.

Excision or aspiration is performed for abscesses greater than 2.5 cm in diameter. Aspiration has become the procedure of choice because it is equally effective and less invasive than excision. Empiric antibiotics should be given based on the expected etiologic agents, presumed route and source of infection, predisposing factors, and adjusted based on the cultures. When the cause is unknown, the patient should receive a third- or fourth-generation cephalosporin, for example, ceftazidime 2 g IV q 8 hr (or ceftriaxone 2 g IV q 12 hr) or penicillin (PCN) G 5 MU IV q 6 hr, and metronidazole 500 mg IV q 6 hr. For paranasal sinus sources, administer PCN and metronidazole. In treatment of posttraumatic cases, administer nafcillin 2 g IV q 2 hr (or vancomycin 1 g IV q 12 hr, if methicillin-resistant S. aureus is suspected) and a third-generation cephalosporin such as ceftazidime 2 g IV q 8 hr. Treatment should be given for 6 to 8 weeks, often followed by additional 2 to 6 months of oral therapy or until the resolution of neuroimaging findings. Three to 4 weeks may be adequate in patients treated with surgical drainage. In human immunodeficiency virus (HIV)-positive patients, coverage should be added for toxoplasmosis with pyrimethamine plus sulfadiazine or clindamycin. Mucormycosis is treated with amphotericin B. Antiepileptic drugs may be given for up to 3 months. Routine corticosteroid administration is controversial and should be used only when mental status is significantly depressed and substantial mass effect can be demonstrated on imaging, and therapy should be of short duration.


Mortality rates range from 5% to 15%. Poor prognosis is associated with very young or old age; anaerobic pathogens; large, multiple, deep, cerebellar, or multiloculated abscesses; acute clinical presentation with stupor/coma; intraventricular or subarachnoid rupture; concomitant pulmonary infection or sepsis; and specific organisms (i.e., Aspergillus and Pseudomonas species, fungal). Long-term sequelae include cognitive deficits (developmental delay in children), seizures, and focal deficits.

Abscess, Epidural


Abscess, epidural, intervention, infection


Spinal epidural abscess (SEA) is an uncommon condition with an estimated incidence of 0.2 to 2.0/10,000 hospital admissions and a peak incidence in the sixth and seventh decades of life. Conditions commonly associated with SEA include diabetes mellitus, intravenous drug misuse, chronic renal failure, alcoholism, and cancer.


The majority of SEAs are thought to result from the hematogenous spread of bacteria usually from a cutaneous or mucosal source with spread to the posterior aspect of the spinal canal. Direct spread from an adjacent source is less common and typically presents within the anterior aspect of the canal. The most common causative organisms are Staphylococcus aureus (57%–73%), Mycobacterium tuberculosis (25%), other gram-positive cocci (10%), gram-negative organisms 18%, and anaerobes 2%.

Clinical features

The initial manifestations of SEA are often nonspecific and include fever and malaise. The classical diagnostic triad consists of fever, spinal pain, and neurologic deficits. However, over time, an untreated abscess may progress from focal back pain, to radicular pain, to neurologic deficits (motor weakness, sensory changes, and bladder or bowel dysfunction), and then paralysis. Once paralysis develops, it may quickly become irreversible. Thus urgent intervention may be required if progression of weakness or other neurologic findings are detected.


Surgical decompression and drainage with systemic antibiotic therapy is the treatment of choice. Empirical antimicrobial must be started early and be delivered intravenously in high doses and immediately following the collection of two sets of blood cultures. Appropriate empiric parenteral regimens include: vancomycin (15–20 mg/kg IV every 8–12 hours. Trough levels should be drawn 30 minutes prior to the next dose) for empiric coverage of methicillin resistant Staphylococcus aureus (MRSA) plus either ceftriaxone (2 g IV q 12 hr) or cefepime (2 g IV q 8 hr) or ceftazidime (2 g IV q 8 hr). Treatment should be continued for at least 4 weeks but may be prolonged for 8 weeks or longer if vertebral osteomyelitis is suspected.


Overall prognosis is poor; 5% die due to uncontrolled sepsis or other complications, irreversible paraplegia occurs in 4% to 22%, and residual motor weakness in 37%.



Acalculia, dyscalculia, aphasia, stroke

Acalculia refers to an acquired computational disability (as opposed to developmental dyscalculia which occurs in 5% of school-age children and is usually associated with dyslexia). The ability to perform mathematical calculations is complex as it requires not only an arithmetic brain center, but also intact attention, language processing, spatial orientation, memory, body knowledge, and executive function.

Acalculia may be classified as either primary or secondary. Primary acalculia (anarithmetia), an acquired isolated defect in comprehending numerical systems, is rare. Notable secondary types due to other cognitive defects are: aphasic, an inability to read or write numbers, usually occurring with left posterior parietal lesions; spatial, a mental misalignment of numbers usually due to right posterior hemispheric lesions; and frontal, due to impaired attention, perseveration, and executive dysfunction.

Acalculia can be part of Gerstmann syndrome (acalculia, agraphia, right-left disorientation, and finger agnosia) due to left angular gyrus lesions. Common causes of acalculia include epilepsy, metabolic or genetic disorders, focal lesions (e.g., stroke, tumor, trauma, or abscess), or commonly as part of a neurodegenerative disease (e.g., dementia). Rehabilitation is treatment of choice, with variable results. Spontaneous recovery is seen in many stroke and trauma patients.


Ardila A., Rosselli M. Acalculia and dyscalculia. Neuropsychol Rev. 2002;12(4):179–231.

Rapin I. Dyscalculia and the calculating brain. Pediat Neurol. 2016;61:11–20.

Acid-Base Disturbances


Respiratory acidosis, respiratory alkalosis, metabolic acidosis, metabolic alkalosis

Respiratory alkalosis

This condition is most frequently observed in patients with hepatic cirrhosis, bronchial asthma, salicylate intoxication, hypoxia, sepsis, pneumonia, and acute anxiety (hyperventilation syndrome). Acute respiratory alkalosis constricts cerebral arterioles and decreases cerebral blood flow. Confusion accompanied by a slow electroencephalogram (EEG) may develop. Symptoms of milder respiratory alkalosis include paresthesias, dizziness, cramps as a result of coexistent tetany, hyperreflexia, and muscle weakness. More severe alkalosis (pH 7.52–7.65) in patients with respiratory insufficiency and hypoxia may result in a symptom complex of hypotension, seizures, asterixis, myoclonus, and coma. Treatment is to correct the underlying cause.

Respiratory acidosis

Acute respiratory acidosis is a condition of low pH and high CO2 concentration, occurring as a result of impairment of the rate of alveolar ventilation. Causes of acute respiratory acidosis include sedative drugs, brainstem injury, neuromuscular disorders, chest injury, airway obstruction, and acute pulmonary disease. Lethargy and confusion occur as the PCO2 rises above 55 mm Hg. Seizures, stupor, or coma may occur with levels greater than 70 mm Hg. The serum bicarbonate level is either normal or high, depending on how rapidly the respiratory failure developed. Neurologic manifestations resulting from cerebral vasodilation include headache, increased intracranial pressure, and papilledema. Hyperreflexia or hyporeflexia and myoclonus may also occur.

Chronic respiratory acidosis generally occurs in patients with chronic obstructive pulmonary disease (COPD), restrictive lung disease (e.g., severe kyphoscoliosis), or extreme obesity (Pickwickian syndrome). It is most often symptomatic with acute exacerbations of disease. Compensatory polycythemia often results from chronic hypercapnic states. Hypoventilation or Pickwickian syndrome may manifest as excessive daytime somnolence.

Therapy of respiratory acidosis involves ventilatory support and treating the underlying disorder. The possibility of sedative or narcotic drug ingestion must be suspected in otherwise healthy patients who suddenly develop acute respiratory depression.

Metabolic alkalosis

Metabolic alkalosis may result from either excessive ingestion of base or excessive loss of acid. Causes of hypokalemic metabolic alkalosis include Cushing syndrome, vomiting or gastric drainage, diuretic therapy, and primary aldosteronism. Neurologic manifestations include paresthesias, cramps (due to tetany), muscle weakness (due to associated hypokalemia), and hyporeflexia. Severe metabolic alkalosis produces a blunted, confused state rather than stupor or coma and may result in cardiac arrhythmias and severe compensatory hypoventilation.

Treatment depends on the underlying cause.

Metabolic acidosis

Metabolic acidosis occurs when a decrease in plasma bicarbonate level lowers pH. Cardinal features are hyperventilation and, when severe, Kussmaul respirations. In chronic metabolic acidosis, hyperventilation may be difficult to detect on clinical examination. The most common causes of metabolic acidosis sufficient to produce coma and hyperpnea include uremia, diabetes, lactic acidosis, and ingestion of acidic poisons. Ketoacidosis occasionally develops in severe alcoholics after prolonged drinking episodes. In diabetics treated with oral hypoglycemic agents, lactic acidosis and diabetic ketoacidosis must be considered.

The presence of neurologic symptoms depends on various factors, including the type of systemic metabolic defect, whether the fall in systemic pH affects the pH of the brain and cerebrospinal fluid (CSF), the rate at which acidosis develops, and the specific anion causing the metabolic disorder. All forms of metabolic acidosis produce hyperpnea as the first neurologic symptom. Other manifestations include lethargy, drowsiness, confusion, and mild, diffuse skeletal muscle hypertonus. Extensor plantar responses occur at a later stage. Stupor, coma, or seizures generally develop only preterminally. Because metabolic acidosis is a manifestation of a variety of different diseases, the treatment varies depending on the underlying process and on the acuteness and severity of the acidosis.

ADEM Disease


ADEM, acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is a monophasic multifocal demyelinating disorder of the CNS, often following infection or vaccination. ADEM is more frequent in children; however, it may occur at any age. The most frequent preceding infections are flulike illnesses, nonspecific upper respiratory tract infections, and gastroenteritis. Although viral etiologies are most common, it can also follow a bacterial infections and, in rare cases, parasitic infections. Postvaccination ADEM is seen in approximately 10% of cases and is most common after measles, mumps, and rubella.

Clinical presentation

Initial presentation may include meningoencephalitis, fever, encephalopathy, seizures, headache, and meningismus. Focal motor or sensory deficits, ataxia, cranial neuropathies, or brain stem pathology may also be seen.

A more severe presentation known as acute hemorrhagic encephalomyelitis may develop.



MRI shows multifocal demyelinating lesions in CNS white matter, with increased signal in T2-weighted and FLAIR images. Lesions may be large, with poorly defined margins, and are often asymmetric. Lesions may enhance with contrast depending on the time of onset. Lesions that are hypointense on T1 argue against the diagnosis.


Lymphocytic pleocytosis and elevated protein are commonly seen; however, CSF studies can be normal.


High-dose intravenous steroids are used based on their efficacy in treating MS relapses. The aim of steroid treatment is primarily to reduce the CNS inflammatory reaction and accelerate clinical recovery.

Methylprednisolone 20 to 30 mg/kg/day in children and 1 g/day in adults for 3 to 5 days, followed by oral prednisolone 1 to 2 mg/kg/day for 1 to 2 weeks, with subsequent tapering over 2 to 6 weeks. The exact duration of steroid taper is not known; however, early discontinuation may convey a higher risk of relapse. IVIG and sometimes PLEX are used as a second line treatment in patients who do not respond to steroids.


In children, ADEM has a favorable prognosis in 60% to 80% of cases. Most children have functional recovery, and severe disability is rarely seen. Mortality is ≤ 5%. Adults have a less favorable prognosis compared with children. Functional recovery is the outcome in 45% to 65% of adult patients. Mortality can be as high as 15%.



Recognition, ventral stream, visual agnosia, auditory agnosia, stroke

This rare condition is characterized by impaired recognition of objects, people, and sounds despite intact primary visual, auditory, and tactile senses. An agnosic patient will be able to sense the presence of an object, but will not be able to apply meaning to the previously recognized object and thus fails to recognize it. Agnosia is seen in a variety of neurologic insults including stroke, tumor, neurodegenerative conditions, and trauma. It is important to demonstrate intact vision, hearing, and sensation modalities before diagnosing agnosia. It is also important to rule out anomic aphasia prior to diagnosing any visual agnosia. In both visual agnosia and anomic aphasia, a patient will not be able to name an object. However, a patient with anomic aphasia will recognize the object.

There are three forms of agnosia:

  1. I. Visual agnosia refers to inability to visually recognize familiar objects. There are two main forms of visual agnosia.

    1. A. The apperceptive type is a deficit of visual processing in which abnormal visual percepts are formed and may occur after bilateral injury to the primary visual cortex. Patients are unable to copy or match visually presented items.
    2. B. The associative type occurs when the deficit occurs after percept formation but before meaning has been associated. Patients may be able to copy objects, but will not recognize them. The majority of these patients have associated achromatopsia.

Object agnosia (inability to recognize objects), prosopagnosia (loss of recognition of specific members of a generic group; distinguishing and recognizing faces, cars, houses, etc.), and achromatopsia (inability to perceive color) are associative visual agnosias occurring with bilateral occipito-temporal lesions. Simultanagnosia is a visual agnosia in which the patient will be able to recognize individual parts of an object or single objects but not a scene as whole. This is seen as part of Balint syndrome of simultanagnosia, optic ataxia, and ocular motor apraxia usually due to bilateral occipito-parietal lesions.

The image in Fig. 1 may be used to detect simultanagnosia. A patient is presented with the image and asked to describe the scene. A normal patient will be able to describe the actions occurring in the scene; however, a patient with simultanagnosia may be able to recognize a few individual objects, but not their relationship to each other.

  1. II. Auditory agnosia refers to an inability to recognize sounds that cannot be attributed to a hearing defect. It may be restricted to nonspeech sounds (selective auditory agnosia) or speech sounds (pure word deafness), or may involve both (generalized auditory agnosia). Thus, a patient may be able to hear a bird chirping, but not recognize that the sound is originating from a bird.
  2. III. Tactile agnosia refers to the inability to recognize objects by the tactile sense, despite intact primary sensation sense (light touch, temperature, pinprick, etc.). The patient usually can visually recognize the object. Astereognosis, an inability to recognize objects placed in the hand, is not well characterized due to the difficulty of separating it from primary sensory loss.

Figure 1
Figure 1 Simultagnosia test.
Simultagnosia is characterized by the inability to recognize two or more things at the same time.

There is also a rare agnosia called anosagnosia that refers to a denial of illness. This may be seen as part of a neglect syndrome with right hemispheric damage. The patient may not recognize a body part, such as an arm, as belonging to the self.


Corrow S.L., Dalrymple K.A., Barton J.J. Prosopagnosia: current perspectives. Eye Brain. 2016;8:165–175.



Agraphia, writing, alexia, frontal lobe, apraxia, aphasia

Agraphia is a neurologic sign resulting in the inability to communicate through writing. The existence of a writing center remains controversial; writing involves multiple functional systems, visual or auditory input processing, language analysis, spatial organization of hand gestures, gesture planning, and highly specific hand movements.

Neuropsychologists and linguists have defined two systems of writing. The phonological system decodes speech sounds (phonemes) into letters. In phonological agraphia, produced by lesions of supramarginal gyrus or the insula medial to it, the patient is unable to spell nonsense words but is capable of spelling familiar words. The lexical system retrieves visual word images when spelling. Lexical agraphia is marked by errors in spelling irregular words, but these errors are phonologically correct (rough spelled as ruf). Lexical agraphia occurs with lesions at the junction of the posterior angular gyrus and parieto-occipital lobule.

Agraphia, “aphasia of writing,” occurs in five clinical forms:

  1. I. Pure agraphia (no other language abnormality present) is rarely seen in pure form. It occurs with lesions of the second frontal convolution (Exner area), superior parietal lobule, and the posterior sylvian region.
  2. II. Aphasic agraphia is the writing disturbance of aphasics that usually resembles their spoken speech.
  3. III. Agraphia with alexia is produced by a dominant angular gyrus lesion. Alexia without agraphia occurs with dominant hemisphere lesions affecting the parieto-occipital region and the splenium of the corpus callosum.
  4. IV. Apractic agraphia, in which production of letters and words is abnormal, usually occurs with a dominant superior parietal lobule lesion.
  5. V. Spatial agraphia with abnormalities of spacing letters and maintaining a horizontal line is usually produced by nondominant parietal lesions.


Lubrano V., Roux F.E., Démonet J.F. Writing-specific sites in frontal areas: a cortical stimulation study. J Neurosurg. 2004;101(5):787–798.

Mesulam M.M. Principles of behavioral and cognitive neurology. New York: Oxford University Press; 2000.



Human immunodeficiency virus, acquired immunodeficiency syndrome, neurological complications, central nervous system disorders, peripheral nervous system disorders


Acquired immunodeficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV), a retrovirus. Neurologic manifestations can occur at any level of the neuraxis at any stage of infection and can be a result of direct HIV infection, HIV-induced immune dysregulation, opportunistic diseases, or pharmacologic therapy for the disease and its complications. Specific syndromes tend to occur more frequently during particular phases of HIV infection (but can appear at almost any point during the course), and virtually all have been described as the initial presenting feature of HIV infection. Coexistent systemic infections are common and should be specifically sought and treated concomitantly. The standard method for diagnosing HIV infection is measurement of antibody by enzyme-linked immunosorbent assay (ELISA) followed by Western blot for confirmation of ELISA-positive samples. Prior to host antibody response (“window period”), HIV antigen tests (e.g., p24 protein antigen) and nucleic acid (RNA, proviral DNA) tests are more sensitive. Rate of disease progression is directly related to HIV RNA levels (viral load).

Major HIV-Associated central nervous system (CNS) disorders classified by neuroanatomic localization


  1. I. Aseptic HIV meningitis
  2. II. Cryptococcal meningitis
  3. III. Tuberculous meningitis
  4. IV. Syphilitic meningitis
  5. V. Listeria monocytogenes meningitis
  6. VI. Lymphomatous meningitis

Brain (Predominantly Nonfocal)

  1. I. HIV-associated dementia (HAD)
  2. II. HIV-associated mild cognitive dysfunction (MCMD)
  3. III. Toxoplasma encephalitis
  4. IV. Cytomegalovirus (CMV) encephalitis
  5. V. Aspergillus encephalitis
  6. VI. Herpes encephalitis
  7. VII. Metabolic encephalopathy (alone or concomitantly)

Brain (Predominantly Focal)

  1. I. Cerebral toxoplasmosis
  2. II. Primary CNS lymphoma (PCNSL)
  3. III. Progressive multifocal leukoencephalopathy (PML)
  4. IV. Cryptococcoma
  5. V. Tuberculoma
  6. VI. Varicella-zoster virus (VZV) encephalitis
  7. VII. Stroke

Spinal Cord

  1. I. Vacuolar myelopathy (VM)
  2. II. CMV myeloradiculopathy
  3. III. VZV myelitis
  4. IV. Spinal epidural or intradural lymphoma (metastatic)
  5. V. Human T-cell lymphotropic virus (HTLV)-1-associated myelopathy

Classification of HIV-Associated neuromuscular disorders

Peripheral Neuropathies

  1. I. Early stages (immune dysregulation)

    1. A. Acute inflammatory demyelinating polyneuropathy (AIDP)
    2. B. Chronic inflammatory demyelinating polyneuropathy (CIDP)
    3. C. Vasculitic myelopathy
    4. D. Brachial plexopathy
    5. E. Lumbosacral plexopathy
    6. F. Cranial mononeuropathy
    7. G. Multiple mononeuropathies

  2. II. Midstage and late stage (HIV-replication driven)

    1. A. Distal sensory polyneuropathy
    2. B. Autonomic neuropathy

  3. III. Late stages (opportunistic infection, malignancy)

    1. A. CMV polyradiculomyelitis
    2. B. Syphilitic polyradiculomyelitis
    3. C. Tuberculous polyradiculomyelitis
    4. D. Lymphomatous polyradiculopathy
    5. E. Zoster ganglionitis
    6. F. CMV mononeuritis multiplex
    7. G. Nutritional neuropathy (vitamins B12, B6)
    8. H. AIDS-cachexia neuropathy
    9. I. Amyotrophic lateral sclerosis (ALS)-like motor neuropathy

  4. IV. All stages (toxic neuropathy)

    1. A. Nucleoside reverse transcriptase inhibitors (didanosine, zalcitabine, Stavudine)
    2. B. Other drugs (vincristine, isoniazid, ethambutol, thalidomide)


  1. I. Polymyositis
  2. II. Pyomyositis
  3. III. Inclusion body myositis
  4. IV. Toxic (zidovudine) myopathy
  5. V. AIDS-cachexia myopathy

Neurologic events in HIV infection

Early HIV Infection

Initial HIV infection usually manifests as a nonspecific viral syndrome of fever, arthralgias, myalgias, and malaise lasting several days. Formed antibodies to HIV proteins take 6 months to appear. Prior to seroconversion, standard anti-HIV antibody assays are negative, and diagnosis can be made only by means of Western blot assay for viral antigen. Several syndromes can be associated with this early phase of infection, and their association with HIV may be discerned only if Western blot is obtained.

  1. I. HIV meningoencephalitis—a viral meningitis can accompany the syndrome of initial infection. In a few patients, this affects the brain parenchyma as well, resulting in a self-limited encephalopathy.
  2. II. Transverse myelitis rarely accompanies acute HIV infection.
  3. III. AIDP, also called Guillain-Barré syndrome (GBS), can occur upon or shortly after initial infection. In cases associated with HIV, there may be a mild CSF pleocytosis; however, this is not always the case. A case series by Thornton et al. found a higher incidence of HIV infection among people with GBS, thus HIV testing of patients with GBS should be considered. Course and treatment of HIV-related GBS are similar to those for idiopathic GBS.
  4. IV. Sensory ganglioneuropathy.
  5. V. Brachial plexitis.
  6. VI. Rhabdomyolysis can accompany initial infection. Steroids can be beneficial.

Midstage HIV Infection (CD4 Count 200–500/μL)

  1. I. HIV meningitis can recur at any point and may remain asymptomatic. The resulting elevated CSF protein and pleocytosis significantly complicates work-up for other infections.
  2. II. CIDP is the chronic form of AIDP. Patients can benefit from intravenous immunoglobulin or plasmapheresis.
  3. III. Mononeuritis multiplex, when apparent in early or midstage HIV infection, is often self-limited.
  4. IV. Nucleoside antiviral polyneuropathy—didanosine, zalcitabine, and stavudine—can all cause a dysesthetic sensory neuropathy, especially at higher doses. Often of subacute onset over weeks, it gradually improves after change of offending agent; both features help to distinguish this from HIV-related distal sensory neuropathy.
  5. V. Inflammatory myopathy presents as proximal muscle weakness and sometimes myalgia. Biopsy shows inflammation. Steroids are beneficial, if immune status permits.
  6. VI. Zidovudine (AZT) myopathy occurs because AZT is a mitochondrial toxin. Presentation is similar to inflammatory myopathy. Biopsy suggests mitochondrial dysfunction but may also show inflammation. Clinical improvement after AZT withdrawal is the best means of diagnosis.

Late HIV Infection (CD4 Count < 200/μL)

  1. I. Focal brain lesions

    1. A. Cerebral toxoplasmosis—caused by intracerebral reactivation of infection with the parasite Toxoplasma gondii, this syndrome is usually manifested in fever, headache, confusion, seizures, and focal neurologic signs, although any or all of these can be lacking. Neuroimaging typically reveals multiple ring-enhancing lesions. Antibiotics are usually quite effective.
    2. B. PCNSL occurs in 2% of AIDS patients. PCNSL is the second most common cause of ring-enhancing lesions on computerized tomography/magnetic resonance imaging (CT/MRI) and is usually unifocal. It can be distinguished from T. gondii by single-photon emission CT (SPECT) or positron emission tomography (PET). Any patient with ring-enhancing lesions that are atypical for toxoplasmosis or do not respond to several weeks of anti-Toxoplasma therapy must undergo biopsy. Mean survival is 1 month from diagnosis without whole-brain radiotherapy and 4 to 6 months with it.
    3. C. Progressive multifocal leukoencephalopathy (PML) results from reactivation of John Cunningham (JC) virus, an infection generally of no consequence to the immunocompetent. Reactivation in oligodendroglia leads to demyelinating white matter disease, focal neurologic deficits, and non–ring-enhancing white matter lesions on scan. Mean survival is 2 to 4 months. Ten percent of patients have enhancing lesions, which may be associated with increased survival. No specific therapy is known, although occasional patients have responded to treatment with cytarabine or cidofovir.
    4. D. Stroke is not a complication of HIV per se, but 4% of AIDS patients have a symptomatic stroke during their lives. Ischemic stroke may be caused by AIDS-related bacterial endocarditis, viral-associated vasculitis, or perivascular infection, or it may be a result of more traditional risk factors such as hypertension and hyperlipidemia; intracranial hemorrhage can complicate PCNSL, metastatic Kaposi sarcoma, or (rarely) toxoplasmosis.
    5. E. Focal brain lesions in AIDS patients can be due to any of the previously mentioned conditions, plus cysticercosis, fungal abscess (due to Candida infection, Aspergillus infection, mucormycosis, coccidioidomycosis, etc.), bacterial abscess (caused by mycobacteria, T. pallidum, Nocardia, Listeria, etc.), or other tumors (glioma, Kaposi sarcoma, other metastases). The usual approach in a patient with typical imaging findings such as a ring-enhancing lesion and positive toxoplasma serologic test is to treat empirically for toxoplasmosis and proceed to biopsy if repeat scan shows no improvement. Those with negative serologic findings or atypical scan should undergo biopsy immediately.

  2. II. Cryptococcal meningitis develops in 10%. It often presents as a combination of cognitive impairment, personality change, lethargy, cranial neuropathies, and increased intracranial pressure, with or without typical signs and symptoms of meningismus. Fungal CSF culture is the “gold standard,” but results take weeks; CSF cryptococcal antigen is rapid and highly sensitive and specific. India ink smear is also rapid and increases sensitivity. Initial treatment should be amphotericin B with flucytosine. Unfortunately, response can be as low as 40%, and recurrence is common; however, in those surviving the initial infection, long-term suppression with daily fluconazole can be effective.
  3. III. Syphilitic meningitis and meningovasculitis frequently complicate HIV infection, because T. pallidum shares some risk factors with HIV. Findings include meningismus, cranial neuropathies, and with chronic infections, classic tertiary syphilis. Diagnosis depends on a combination of serologic testing and clinical suspicion. Treatment is with penicillin.
  4. IV. Tuberculous meningitis is more common in AIDS patients than in those who are not immunosuppressed. Tuberculomas may also rarely occur. CSF polymerase chain reaction (PCR) can complement culture.
  5. V. HIV encephalopathy (AIDS dementia complex, HAD) is a subcortical dementia of unclear pathogenesis characterized by cognitive slowing, emotional blunting, and motor impairment. Prevalence estimates vary widely (5%–60%); in the pediatric population, the prevalence is much higher (90%). Work-up consists of ruling out treatable infections (cryptococcus, syphilis, CMV encephalitis) and medical conditions (hypothyroidism, vitamin B12 deficiency). No specific treatment beyond antiviral therapy is known.
  6. VI. VM is present in up to 55% on autopsy but symptomatic in far fewer. It is of uncertain pathogenesis, and pathologic findings include vacuolization in the dorsal and lateral columns of the spinal cord. Symptoms, which develop late, include constipation, urinary disturbances, ataxia, and spastic paraparesis. There is no treatment. The process is painless and slowly progressive; pain or rapid progression should prompt evaluation for other causes, such as viral myelitis, metastatic cord compression, or epidural abscess. Other subacute myelopathies sometimes associated with AIDS include syphilis and vitamin B12 deficiency.
  7. VII. Mononeuritis multiplex in late HIV infection is often due to CMV and benefits from ganciclovir. CMV can also cause encephalitis, meningitis, retinitis, myelitis, or polyradiculitis. CSF PCR for central nervous system CMV infections has approximately 90% sensitivity.
  8. VIII. VZV can cause encephalitis, Ramsay-Hunt syndrome, myelitis, vasculitis, and segmental zoster rashes (shingles). Herpes simplex virus (HSV) can cause encephalitis or myelitis. Both HSV and VZV are treated with acyclovir.
  9. IX. Distal symmetric polyneuropathy is an axonal, predominantly sensory neuropathy with impairment of all sensory modalities, often with paresthesias, which can be painful. Tricyclic antidepressants and anticonvulsants can help dysesthetic symptoms, but some patients may require opiates. Capsaicin may also help.

All Stages

  1. I. HIV-related meningitis: aseptic (acute or recurrent) or chronic
  2. II. Asymptomatic CSF abnormalities: elevated protein, lymphocytic pleocytosis, normal glucose
  3. III. Nucleoside neuropathy and zidovudine myopathy
  4. IV. Inflammatory myopathy

For more information

www.cdcnpin.org (epidemiologic data)

www.cc.nih.gov/phar/hiv-mgt. (consensus panel reports on treatment of HIV infection)


Bhatia N.S., Chow F.C. Neurologic complications in treated HIV-1 infection. Curr Neurol Neurosci Rep. 2016;16(7):62.

Bradley W.G., Daroff R.B., Fenichel G.M., Jankovic J. Neurology in clinical practice, ed 4. Philadelphia: Butterworth-Heinemann; 2004.



Alcohol, withdrawal, neuropathy, myopathy, Wernicke-Korsakoff, encephalopathy, Marchiafava-Bignami

Neurologic effects of alcohol are due to a combination of its direct neurotoxic effects, its metabolites, nutritional factors, and genetic predisposition. Neurologic complications associated with alcohol abuse can be conceptually divided into the following five categories (Table 1):

  1. I. Intoxication: Acute intoxication with alcohol correlates roughly with blood concentrations. Cognitive dysfunction tends to occur early, and cerebellar, autonomic, and vestibular symptoms tend to occur at higher blood levels. Positional vertigo may result from alcohol diffusing into the cupula when the recumbent position is assumed. As the alcohol concentration rises to a certain level, the intoxication is greater than when it falls to the same level. Blackouts are periods of amnesia, usually during binge drinking, and occur in persons with and without alcohol dependence.
  2. II. Withdrawal syndromes: These occur in individuals with alcohol dependency resulting from either decreased intake or abrupt cessation of drinking. The syndromes may be early or late. Most common are the early symptoms, which begin 12 to 24 hours after decreased intake. Tremulousness is common and may be accompanied by nausea, vomiting, insomnia, and hallucinations (visual, tactile, or auditory). Treatment consists of benzodiazepines. Auditory hallucinations may persist, necessitating the use of neuroleptics.

Withdrawal seizures are always generalized tonic-clonic and begin within the first 24 hours but may occur after several days. Focal seizures should not be attributed to alcohol withdrawal and should warrant further investigation including computed tomography (CT) of head to rule out any structural abnormality.

Treatment of withdrawal seizures is controversial because they are usually self-limited. Initial loading with phenytoin and slowly tapering off after several days is one approach. Thiamine is routinely given and hypomagnesemia, if present, is treated.

Delirium tremens is the most severe, deadly complication of withdrawal and has a peak incidence 72 to 96 hours after decreased alcohol intake. Confusion, agitation, vivid hallucinations, tremors, and increased autonomic activity (tachycardia, fever, sweating, and hypertension or orthostatic hypotension) are characteristic. These symptoms can last 1 to 3 days and can be fatal (~ 10%). Treatment consists of sedation with benzodiazepines, hydration with intravenous (IV) fluids, and administration of thiamine, multivitamins, and magnesium (if indicated). Autonomic hyperactivity should be treated aggressively if present.

  1. III. Wernicke-Korsakoff syndrome: This is the most common deficiency syndrome due to chronic alcoholism. Wernicke syndrome, or Wernicke encephalopathy, is reversible and represents the acute phase presentation with the triad of encephalopathy, ataxia, and oculomotor disturbance (nystagmus, ophthalmoplegia, and gaze palsy). However, a complete triad of signs is often not present. Atrophy of the mammillary bodies is common. Korsakoff syndrome, which is irreversible, is a more chronic condition and includes anterograde amnesia (the inability to incorporate ongoing experience into memory) leading to confabulation. Both syndromes are attributed to thiamine deficiency and can also be seen in non-alcoholic malnutrition states, although much less commonly. Treatment consists of IV thiamine 500 mg three times daily for two days, then 250 mg intravenous (IV) or intramuscular (IM) for five days, then oral thiamine indefinitely. IV glucose should never be given without thiamine to a chronic alcoholic because of the risk of precipitating Wernicke encephalopathy. As with most alcohol-related syndromes, supplemental vitamins and magnesium may be beneficial.
  2. IV. Other alcohol-related syndromes: These include cerebellar degeneration, peripheral neuropathy, optic neuropathy, and myopathy.

Cerebellar degeneration invariably involves the anterior and superior cerebellar vermis and paravermian regions with resultant truncal and gait ataxia. Limb ataxia, if present, is much milder than truncal ataxia and more severe in the legs than in the arms.

Chronic peripheral neuropathy, which can involve both sensory and motor nerves, is usually heralded by complaints of numb, burning feet involving distal limbs symmetrically. Minor motor signs may evolve. Pathogenesis seems to involve both toxic alcohol effects as well as poor nutrition status. Abstinence from alcohol is paramount for treatment success.

Nutritional amblyopia (previously called tobacco-alcohol amblyopia) consists of gradual visual loss over a period of several weeks and is caused by selective lesion of the optic nerves secondary to poor nutrition and is not a direct toxic effect of alcohol. Treatment with a combination of adequate diet and B vitamins, despite the continuation of drinking and smoking, results in visual recovery.

Alcoholic myopathy is believed to be caused by the toxic effects of alcohol and improves with abstinence. It may occur as an acute necrotizing disorder with muscle pain and rhabdomyolysis, or as a more slowly progressive disease with proximal weakness. The combination of thiamine, multivitamins, and abstinence is the treatment of choice for these syndromes.

  1. V. Conditions of somewhat uncertain etiology: Additional syndromes occurring in chronic alcoholics include central pontine myelinolysis, Marchiafava-Bignami syndrome, and cortical atrophy.

Central pontine myelinolysis is a rare cerebral white matter disorder, associated with basis pontis lesions with resultant progressive quadriparesis, horizontal gaze palsy, and obtundation leading to coma. It occurs with excessively rapid correction of hyponatremia.

Marchiafava-Bignami syndrome is a rare demyelinating disease of the corpus callosum and adjacent subcortical white matter, sometimes associated with excessive consumption of crude red wine. Patients can have cognitive impairment that resembles a frontal lobe or dementia syndrome, spasticity, dysarthria, and impaired gait. The CT scan appearance of “atrophy” or “parenchymal volume loss” is probably related to fluid shifts in the brain and may reverse with abstinence.

Alcoholics have an increased incidence of stroke related to a variety of factors, including rebound thrombocytosis, altered cerebral blood flow, and hyperlipidemia.


Bradley W.G., Daroff R.B., et al. Neurology in clinical practice, ed 4. Philadelphia: Butterworth-Heinemann; 2004.

Keil V.C., Greschus S., Schneider C., Hadizadeh D.R., Schild H.H. The whole spectrum of alcohol-related changes in the CNS: practical MR And CT imaging guidelines for daily clinical use. Rofo. 2015;187(12):1073–1083.



Alexia, agraphia, aphasia, dyslexia, Gerstmann syndrome, Dejerine

Alexia denotes a group of acquired disorders of reading, which helps to distinguish it from the more common syndrome of dyslexia. Reading uses neural networks, including the occipital cortex for perception of visual language, and the heteromodal association cortex of the angular gyrus for processing into auditory language.

Alexia occurs in three main forms:

Alexia without agraphia (pure alexia). This form was described first by Dejerine in 1892. As if blindfolded, the patient loses the ability to read but can still write. This is seen with left occipital lesions (e.g., left posterior cerebral artery (PCA) infarct, tumors, abscess), usually affecting the splenium of the corpus callosum. All visual information must be processed by the right occipital lobe because the left is damaged (Fig. 2). However, this information cannot pass from the right visual area to the left language centers due to injury of the splenium. As such, there is associated right hemianopia or superior quadrantanopsia and impaired color naming (achromatopsia). Further deficits involve short-term memory for visual language elements or an inability to process multiple letters at once (simultagnosia).

Figure 2
Figure 2 Horizontal brain diagram of pure alexia without agraphia. From Kirshner, H. S.: Aphasia and aphasic syndromes. In Daroff, R. B., Jankovic, J., Mazziotta, J. C., & Pomeroy, S. L. (Eds.), (2016). Bradley’s neurology in clinical practice, ed 7. Philadelphia: Elsevier, pp 128–144.e2. Figure 13-6.

Alexia with agraphia. The patient loses the ability to read and write. This is seen most often with left middle cerebral artery (MCA) stroke or mass lesion affecting the left inferior parietal lobule, especially the angular gyrus. In addition to alexia with agraphia, the patient may also display the entire Gerstmann syndrome of agraphia, acalculia, left-right disorientation, and finger agnosia. There may also be a right homonymous hemianopia, and mild receptive Wernicke-type aphasia.

Aphasic alexia. This form of alexia is secondary to underlying severe aphasia (language processing) including Broca or Wernicke aphasia. Depending on the subtype of aphasic alexia, different components of reading and language processing will be affected. The four main subtypes include “letter-by-letter” (equivalent to pure alexia), “deep dyslexia” (reading/recognizing only familiar words like concrete nouns and verbs, independent of length; commonly with severe aphasia), “phonological dyslexia” (reading/recognizing familiar words, with failure of comprehension), and “surface dyslexia” (able to piece together nonsense syllables to make words but unable to simply recognize words at a glance; cannot process words with silent letters).


Daroff R.B., Jankovic J., Mazziotta J.C., Pomeroy S.L. Bradley’s neurology in clinical practice, ed 7. Philadelphia: Elsevier; 2016.

Amaurosis fugax


Monocular vision loss, ischemic stroke, carotid disease, transient, ocular disease

Amaurosis fugax (AFx) refers to a transient loss of vision in one or both eyes. The term “amaurosis fugax” has classically been used to imply a vascular cause for the vision loss, but the term continues to be used to describe transient visual loss from any origin. Ischemia is the most common cause of transient monocular vision loss. Other causes include ocular disease including papilledema, optic neuropathy, and increased intraocular pressure. Migraine is the most common cause of bilateral transient visual loss. Other causes include visual seizures and vertebrobasilar ischemia. AFx due to ischemia has a short duration (seconds to minutes) and usually consists of negative symptoms (blackness or graying of the visual field) with an occasional positive phenomenon (scintillating scotomas or points of light). Funduscopic examination may show the cholesterol emboli (Hollenhorst plaques). Embolization from the internal carotid artery, aorta, or heart may be the cause (Table 2).

Aug 12, 2020 | Posted by in NEUROLOGY | Comments Off on A
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