Mark Mumenthaler, M.D., Heinrich Mattle, M.D. Fundamentals of Neurology. – P.113, 115, 116-117, 150-151, 155.
Etiology. Syphilis is caused by the sexually transmitted spirochete, Treponema pallidum.
Clinical manifestations. Hematogenous spread of treponemes in the secondary phase of syphilis may lead to meningeal irritation or early syphilitic meningitis with cranial nerve palsies (basal meningitis). In the tertiary phase (usually one or two years after the primary infection and secondary seeding of treponemes), cerebrospinal syphilis mainly affects the mesenchymal structures (blood vessels, meninges) of
the brain and, often, the spinal cord. Inflammatory changes of vascular walls, particularly in the arteries of the skull base and the middle cerebral a., cause stenoses and multiple ischemic strokes. Meningitis, mainly in the region of the skull base, presents with fluctuating headache and cranial nerve palsies. Occasionally, tertiary syphilis gives rise to polyneuropathic and polyradicular manifestations. In the rare gummous variant of tertiary syphilis, large granulomatous masses may form within
the cranial cavity, producing mass effect and intracranial hypertension. In the quaternary phase of syphilis, the inflammatory process extends into the parenchyma of the brain and spinal cord, producing tabes dorsalis (spinal cord involvement) and/or progressive paralysis (chronic meningoencephalitis).
Tabes dorsalis appears in 7% of untreated syphilitics eight to 12 years after the primary infection. It is characterized, above all, by progressive degeneration of the posterior columns and posterior roots. Its clinical manifestations include progressively severe ataxia, lancinating pains, bladder dysfunction, diminished reflexes, loss of pupillary reactivity, diminished sensitivity to pain, hypotonia of the musculature, and joint deformities.
Progressive paralysis appears 10−15 years after the primary infection and is caused by parenchymal meningoencephalitis with formation of caseating granulomas. Its major clinical sign is progressive dementia, with typical features including impaired judgment, lack of social inhibition, and, in some patients, expansive agitation (megalomania, nonsensical and delusional ideas). In other cases, patients may develop flattening of drive and affect, become depressed, or manifest schizophreniform phenomena (hallucinations, paranoia). The two late forms of neurosyphilis can also be present in combination.
Diagnostic evaluation. The diagnosis of neurosyphilis is established by various serologic tests: the TPHA and FTA−ABS tests for the demonstration of previous contact with Treponema pallidum, the VDRL test for the assessment of current disease activity (though this test is not specific for Treponema pallidum), and the S-IgM test for the demonstration of treponeme-specific IgM antibodies, which indicate an active or florid infection. Neurosyphilis also causes an inflammatory CSF picture with elevated leukocyte count and protein concentration, a positive VDRL test in the CSF, and an elevated CSF concentration of treponeme-specific IgG.
Treatment. All forms of neurosyphilis are treated with penicillin G; if the patient is allergic to penicillin, tetracycline or erythromycin can be given instead. The success of treatment depends on the time at which it is begun: improvement is less likely if the brain and spinal cord parenchyma have already sustained considerable damage.
Prognosis. The prognosis of early syphilitic meningitis is good. In the other phases of neurosyphilis, progression can be prevented by appropriate treatment, but residual deficits are common.
HIV Encephalitis and Opportunistic Infections in
Nearly 50% of persons infected with HIV have a clinically evident infection of the brain or other parts of the nervous system at some point in the course of their illness. The nervous system can be infected with HIV itself, other, opportunistic pathogens, or both. In severe cases, patients may suffer from encephalitis, myelopathy, mono- and polyneuropathy, and/or myopathy. Encephalitis presents with neuropsychological abnormalities including delirium, personality change, and dementia.
Etiology.Mycobacterium tuberculosis bacilli reach the meninges by hematogenous spread, either directly from a primary complex (early generalization), or else from a focus of tuberculosis in an internal organ (late generalization). The site of origin may be clinically silent.
Clinical manifestations.Meningitic symptoms usually develop gradually. Febrile bouts and general symptoms (see above) are often but not always present. Because the infectious process typically centers on the base of the brain (so-called basal meningitis, in contrast to bacterial meningitis, which is typically located around the cerebral convexities), cranial nerve palsies are common, particularly of the nerves of eye movement and the facial n. Moreover, arteritis of the cerebral vasculature may result in focal brain infarction. The protein concentration in CSF is typically markedly elevated and gelatinous exudates in the subarachnoid space, including the basal cisterns, cause progressive hardening of the meninges and malresorptive hydrocephalus.
Diagnostic evaluation. The most important part of the evaluation is the detection of the causative organism in the CSF or other bodily fluids (sputum, tracheal secretions, gastric juice, urine). In the past, the detection of mycobacteria in the CSF often required weeks of culture; at present, it can be done relatively quickly with PCR. Occasionally, a Ziehl−Neelsen stain of the CSF will directly and immediately reveal acid-fast bacilli (mycobacteria).
Treatment generally begins with a combination of four tuberculostatic drugs (isoniazid, rifampicin, pyrazinamide, and myambutol), followed by a combination of three drugs, and then of two, for at least 12 months. Untreated tuberculous meningitis is lethal.
Infectious and Inflammatory Diseases of the Spinal Cord
The spinal cord and spinal nerve roots, like the brain, can be infected by bacteria, viruses, and other pathogenic organisms. Combined infection of the brain and spinal cord is common: simultaneous manifestations of encephalitis, meningitis, myelitis, and radiculitis can be
caused by spirochetes (borrelia, leptospira, treponemes) and by many viruses.
Acute anterior poliomyelitis, on the other hand, affects only the motor neurons of the anterior horns of the spinal cord.
Any infectious or inflammatory disease of the spinal cord, whatever its etiology, is called myelitis. The causes of myelitis include direct infection, secondary autoimmune processes in the wake of an infectious disease, and chronic autoimmune inflammatory disease of the
central nervous system, such as multiple sclerosis. The main causes of acute myelitis include viruses (measles, mumps, varicella-zoster, herpes simplex, HIV), as well as rickettsiae and leptospira. Postvaccinal and postinfectious myelitis have also been described, as has myelitis in the setting of granulomatous disease.
The clinical manifestations range from progressive spastic paraparesis to partial spinal cord transection syndrome. Myelitis can be visualized by MRI (Fig. 7.11).
Transverse myelitis affects the entire cross-section of the spinal cord, producing a complete spinal cord transaction syndrome. It has a variety of causes. Often, the neurological manifestations are preceded by nonspecific flulike symptoms one to three weeks before onset. The spinal cord deficits usually arise acutely or subacutely and become maximally severe within a few days. Fever, back pain, and myalgia accompany the acute phase. The cerebrospinal fluid displays inflammatory changes (lymphocytic pleocytosis, elevated IgG and total protein concentrations). A neuroimaging study (usually MRI) must be performed to rule out a mass or ischemic event. The responsible organism is treated specifically if it can be identified; otherwise, only symptomatic treatment can be given. The spinal cord transection syndrome persists, or resolves less than completely, in two-thirds of all patients.
Acute Anterior Poliomyelitis
Etiology and epidemiology. This disease, caused by a poliovirus, almost exclusively affects the motor neurons of the anterior horn of the spinal cord. Its incidence in countries with a well-developed public health system has been reduced nearly to zero by prophylactic vaccination. The disease is transmitted by the fecal−oral route under conditions of poor sanitation.
Clinical manifestations. After an incubation period ranging from three to 20 days, nonspecific prodromal manifestations arise, consisting of fever, flulike symptoms, and, in some patients, meningeal signs. The prodrome may resolve without further consequence or be followed, within a few days, by a paralytic phase (likewise accompanied by fever). Over the course of a few hours or days, flaccid paralysis arises in various different muscles or muscle groups; it is asymmetrical, often mainly proximal, and of variable extent and severity.
There is no sensory deficit, but the affected muscles may be painful and tender.
Diagnostic evaluation. The diagnosis is based on the typical course and physical findings, combined with an inflammatory CSF pleocytosis: at first, there are several hundred cells per microliter, often mainly polymorphonuclear granulocytes. Later, there is a transition to a predominantly lymphocytic picture. The responsible organism (poliovirus) can be identified in the patient’s stool.
Treatment. There is no specific etiologic treatment; the most important aspect of treatment is the management of respiratory insufficiency (if present).
Prognosis. Brain stem involvement and respiratory paralysis confer a worse prognosis; in the remainder of patients, paralysis may regress partially or completely in a few weeks or months. There is usually some degree of residual weakness.
Postpolio syndrome. This term refers to two different syndromes. Some authors use it for a symptom complex seen a few years after the acute illness in polio patients with residual weakness, characterized by fatigability, respiratory difficulties, pain, and abnormal temperature regulation (with negative polio titers). Others use it for a syndrome with progressive worsening of residual weakness occurring decades after the acute illness. Before this problem can be ascribed to the earlier polio infection, other possible causes of weakness must be ruled out, e. g., compression of the spinal cord or spinal nerve roots because of secondary degenerative disease of the spine.
Amyotrophic Lateral Sclerosis (ALS)
This disease, also known as motor neuron disease (MND), is characterized by combined degeneration of the first and second motor neurons. Its clinical features are thus a combination of flaccid paresis, muscular atrophy, and spasticity.
Epidemiology. Three-quarters of patients are men, most of them between the ages of 40 and 65. More than 95% of cases are sporadic; the rare familial cases are thought to be due to a defect of the Cu/Zn superoxide dismutase gene. Neuropathological hallmark of this disease is loss of anterior horn cells, combined with degeneration of the pyramidal and corticobulbar tracts and of the Betz pyramidal cells of the precentral gyri.
Characteristic clinical manifestations are:
_ weakness and atrophy of the muscle groups of the limbs and trunk (including the respiratory apparatus) and/or the bulbar muscles (tongue, throat), progressing slowly over months,
_ exaggerated reflexes,
_ (in some patients) pyramidal tract signs,
_ intact sensation,
_ often muscle cramps and pain.
Course. At first, there is circumscribed, asymmetrical, predominantly distal muscle atrophy, which is usually most obvious in the intrinsic muscles of the hands. There may be accompanying pain or fasciculations, which are often evident only on prolonged observation. As the disease progresses, muscle atrophy spreads proximally. Spasticity gradually appears as well; it is usually only mild at first and may indeed remain so over the ensuing course of the disease. The intrinsic muscle reflexes are usually brisk, more than one would expect in view of the concomitant atrophy and weakness, but pyramidal tract signs are not necessarily demonstrable. The bulbar muscles are also involved in about 20% of patients, as manifested by atrophy, weakness, and fasciculations of the tongue (Fig. 7.15), dysarthria, and dysphagia (true bulbar palsy). Involvement of the corticobulbar tracts is indicated by exaggerated nasopalpebral, perioral and masseteric reflexes, and by involuntary laughter and crying, which are often present.
Treatment.Riluzole marginally slows the progression of the disease. There is no other specific treatment.
Prognosis. ALS takes a chronically progressive course. Death usually ensues within one or two years, although a minority of patients survives longer.