Diagnosis and management of acute encephalitis.

Encephalitis is typically viral (approximately half of diagnosed cases) or autoimmune (about a quarter) with the remainder remaining undiagnosable at this time. All require general supportive care but only a minority requires intensive care admission - in these intubation, to protect the airway or to treat status epilepticus with anesthetic drugs, may be needed. In some dysautonomia with wide blood pressure fluctuations is the principal concern. Remarkably, in addition to supportive care, specific treatment options are available for the majority - immune-modulating therapy for those with autoimmune disorders, antiviral therapy for herpes simplex 1 and 2, and varicella-zoster encephalitis. Flavivirus infections (West Nile, Japanese encephalitis, tick-borne encephalitis) remain the most common other identified cause of encephalitis but no specific intervention is available. Overall long-term outcomes are favorable in the majority of patients with encephalitis, a proportion that hopefully will improve with further advances in diagnostic technology and therapeutic interventions.

Nervous system Lyme disease.

Lyme disease, the multi-system infection caused by the tick-borne spirochaete Borrelia burgdorferi, can involve the nervous system, most commonly causing, alone or in combination, lymphocytic meningitis or abnormalities of cranial or peripheral nerves, the latter most typically presenting as a painful radicular syndrome. Diagnosis is based on appropriately used, standard serological tests; in instances where the central nervous system is involved, cerebrospinal fluid assessment for organism-specific antibodies can be useful. Treatment with any of several standard regimens of oral or parenteral antimicrobials is highly effective. Prolonged treatment beyond four weeks is rarely if ever warranted, and carries significant risk.

Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To provide evidence-based recommendations on the treatment of nervous system Lyme disease and post-Lyme syndrome. Three questions were addressed: 1) Which antimicrobial agents are effective? 2) Are different regimens preferred for different manifestations of nervous system Lyme disease? 3) What duration of therapy is needed? METHODS: The authors analyzed published studies (1983-2003) using a structured review process to classify the evidence related to the questions posed. RESULTS: The panel reviewed 353 abstracts which yielded 112 potentially relevant articles that were reviewed, from which 37 articles were identified that were included in the analysis. CONCLUSIONS: There are sufficient data to conclude that, in both adults and children, this nervous system infection responds well to penicillin, ceftriaxone, cefotaxime, and doxycycline (Level B recommendation). Although most studies have used parenteral regimens for neuroborreliosis, several European studies support use of oral doxycycline in adults with meningitis, cranial neuritis, and radiculitis (Level B), reserving parenteral regimens for patients with parenchymal CNS involvement, other severe neurologic symptomatology, or failure to respond to oral regimens. The number of children (> or =8 years of age) enrolled in rigorous studies of oral vs parenteral regimens has been smaller, making conclusions less statistically compelling. However, all available data indicate results are comparable to those observed in adults. In contrast, there is no compelling evidence that prolonged treatment with antibiotics has any beneficial effect in post-Lyme syndrome (Level A).

Nervous system Lyme disease.

Lyme disease is a multisystem infectious disease caused by tick-borne spirochetes of the Borrelia burgdorferi group. The disease occurs primarily in specific areas of North America, Europe and Asia, reflecting the distribution of the hard-shelled Ixodes ticks that are required for disease transmission. Diagnosis of this infection can be somewhat problematic, although in clinically appropriate settings, serologic testing can be highly useful, particularly if Western blots are used to confirm borderline or positive results. The organism has several specific organotropisms-involvement of the heart, joints and nervous system being particularly common. The nervous system can be involved in one or more ways. Early in infection, patients tend to get a lymphocytic meningitis, cranial neuritis (particularly the facial nerves) or a painful radiculitis. Rarely, an encephalomyelitis can occur. In patients with more protracted and indolent involvement, a more disseminated mononeuropathy multiplex may occur, or a mild, non-focal alteration of cognitive function and memory, i.e. an encephalopathy. In patients with central nervous system involvement, the most sensitive diagnostic test is the demonstration of intrathecal production of anti-Borrelia burgdorferi antibody. Culture, polymerase chain reaction and other techniques appear to be less specific. In most instances, the disease is quite responsive to antimicrobial therapy. Oral treatment with doxycycline has been shown to be effective in meningitis. In more serious cases two to four week courses of parenteral ceffriaxone or cefotaxime are effective in the vast majority of patients.

Neuroborreliosis: central nervous system involvement.

Despite rapid dissemination of Borrelia burgdorferi throughout the body following initial inoculation, the clinical manifestations of this illness tend to involve specific organ systems preferentially. The nervous system, in particular, is frequently affected; involvement usually follows one of several distinct patterns. Most commonly, patients develop a lymphocytic meningitis, radiculoneuritis or cranial neuropathy, occurring singly or in combination. Patients with radicular involvement often have a myelopathic component as well. At the other extreme, rare patients will develop focal inflammation of the central nervous system, an encephalomyelitis, that appears to involve white matter more often than grey. More commonly, patients may develop cognitive and memory impairment-a mild encephalopathy. In some patients this may represent a subtle form of encephalomyelitis, while in others it is probably a "toxic-metabolic" effect of systemic infection. Disease variability among patients probably is the result of multiple factors, including bacterial strain differences in virulence and organotropism, inoculum size, host immunity, and simultaneous co-infection with other tick-borne organisms. Accurate diagnosis remains somewhat problematic. The cerebrospinal fluid is almost always abnormal in the presence of active CNS infection. Intrathecal production of specific antibody can be demonstrated in over 90% of patients with meningitis or frank inflammatory encephalomyelitis; in patients with a milder encephalopathy this is less consistently observed. In most instances, diagnosis relies on a combination of demonstration of a specific immune response, and clinical judgment. In patients in whom the diagnosis is secure, appropriate antimicrobial therapy is highly effective in the vast majority of cases, although if there has been significant structural damage to the CNS, some residua may remain.

Neuroborreliosis.

Lyme disease is a multisystem infectious disease with frequent nervous system involvement. It affects peripheral nerves, the meningeal lining of the central nervous system (CNS), and the CNS parenchyma, but the underlying pathophysiology remains unclear. Considerable data suggest that dividing Lyme neuroborreliosis into early and late disease stages, as has been done with syphilis--the other well-known spirochetosis that affects the nervous system--lacks pathophysiologic validity. Early CNS seeding has been demonstrated, however, and lymphocytic meningitis and facial paralysis tend to occur relatively early in infection, although radiculoneuropathy and cranial neuropathies may also occur later. Less fulminant forms of peripheral nerve or CNS involvement may present later in the disease course. Encephalomyelitis may occur early or late but is rare; encephalopathy is far more common and tends to occur in patients with evidence of systemic (but not necessarily CNS) Lyme disease. Diagnosis of CNS infection has been difficult, and most studies have relied on indirect methods. Demonstration of intrathecal production of anti-Borrelia burgdorferi antibodies provides the strongest evidence, but correction for the amount of peripheral blood immunoreactivity to B. burgdorferi that crosses the blood-brain barrier is essential. Newer technologies have been applied in an effort to improve detection of B. burgdorferi itself--polymerase chain reaction may provide a sensitive tool for organism detection to complement immunologic techniques. The optimal treatment regimen for Lyme disease has not been defined, but a course of ceftriaxone (2 g/day) or cefotaxime (6 g/day) for 3-4 weeks is commonly prescribed. Intravenous penicillin and oral doxycycline (200 mg/day) for 2 weeks have been used successfully to treat Lyme meningitis, but these results require confirmation.

Neuropathic findings in oculopharyngeal muscular dystrophy. A report of seven cases and a review of the literature.

We describe seven patients with clinical evidence of oculopharyngeal muscular dystrophy. Four of these patients were members of the same Italian-American family. The age at onset was after the fourth decade in all patients. All seven patients had extraocular muscle involvement, and six of the seven patients had clinical, electrophysiological, and/or pathological evidence of neuropathy in addition to features that were suggestive of myopathy. An autopsy was performed on one patient. We discuss the significance of the concurrence of neuropathic features with oculopharyngeal muscular dystrophy in relation to these patients and previously reported cases.

Lyme borreliosis in Bell's palsy. Long Island Neuroborreliosis Collaborative Study Group.

Lyme borreliosis (LB) causes a range of neurologic manifestations, the most common of which is facial nerve paralysis. To evaluate nervous system LB, we organized a neurologic collaborative study group in Suffolk County, NY, a region of high LB incidence. Between July and September 1989, LB serologies were performed on all patients with new-onset Bell's palsy. Seven of 32 had serologic evidence of LB at onset. One, initially seronegative, was highly seropositive 5 weeks later. In the five in whom we examined CSF, there was no evidence of intrathecal synthesis of specific antibody. In highly endemic areas, LB may be responsible for 1/4 of cases of Bell's palsy. Rarely, the palsy may occur prior to the development of a measurable antibody response, indicating a need for follow-up serologic testing.

Familial bilateral carpal tunnel syndrome: report of two families.

Cases of familial carpal tunnel syndrome without other associated conditions are rare. We report two families in which multiple members had bilateral carpal tunnel syndromes. The pattern was consistent with autosomal dominant inheritance. Electrophysiologic studies were performed on nine of the 15 patients, and they demonstrated bilateral pathology of the median nerves at the wrist in all but one patient, without evidence for subclinical, generalized peripheral neuropathy. Quantitative sensory testing was performed in two cases, and it corroborated the absence of peripheral neuropathy. Five of the six patients who underwent carpal tunnel release improved after surgery.

PCR detection of Borrelia burgdorferi DNA in cerebrospinal fluid of Lyme neuroborreliosis patients.

We used the polymerase chain reaction (PCR), a method useful in the detection of Borrelia burgdorferi in vitro, to evaluate CSF in patients thought to have neuroborreliosis. Nested pairs of oligonucleotide primers were designed to recognize the C-terminal region of B burgdorferi OspA. CSF samples were obtained from (1) patients with immunologic evidence of systemic B burgdorferi infection and clinical manifestations suggestive of CNS dysfunction, (2) seronegative patients with clinical disorders consistent with Lyme borreliosis, and (3) patient and contamination controls; all were analyzed in a blinded fashion. PCR detected B burgdorferi OspA DNA in CSF of (1) 10 of 11 patients with Lyme encephalopathy, (2) 28 of 37 patients with inflammatory CNS disease, (3) seven of seven seronegative patients with Lyme-compatible disorders, and (4) zero of 23 patient controls. Zero of 83 additional contamination controls were PCR-positive. In eight patients from whom we obtained CSF before and after parenteral antimicrobial therapy, PCR results invariably predicted clinical outcome accurately.

Nervous system Lyme borreliosis--revisited [corrected; erratum to be published].

A great deal of confusion surrounds the diagnosis, clinical phenomenology, and treatment of Lyme borreliosis. Most diagnostic methods currently in use are indirect and do not differentiate between prior exposure and current infection. A critical review of the literature permits the characterization of a distinct set of neurologic disorders that are almost certainly caused by this infection and their differentiation from the plethora of syndromes that have been anecdotally linked to infection, but in which causality has never been established. This article describes the range of clinical disorders associated with Lyme borreliosis, provides an overview of current approaches to diagnosis, and reviews current treatment protocols.

Neuroactive kynurenines in Lyme borreliosis.

Although neurologic dysfunction occurs frequently in patients with Lyme borreliosis, it is rarely possible to demonstrate the causative organism within the neuraxis. This discordance could arise if neurologic symptoms were actually due to soluble neuromodulators produced in response to infection. Since immune stimulation is associated with the production of quinolinic acid (QUIN), an excitotoxin and N-methyl-D-aspartate (NMDA) agonist, we measured levels of CSF and serum QUIN, and lymphokines. Samples were obtained from 16 patients with CNS Borrelia burgdorferi infection, eight patients with Lyme encephalopathy (confusion without intra-CNS inflammation), and 45 controls. CSF QUIN was substantially elevated in patients with CNS Lyme and correlated strongly with CSF leukocytosis. In patients with encephalopathy, serum QUIN was elevated with corresponding increments in CSF QUIN. Lymphokine concentrations were not consistently elevated. We conclude that CSF QUIN is significantly elevated in B burgdorferi infection--dramatically in patients with CNS inflammation, less in encephalopathy. The presence of this known agonist of NMDA synaptic function--a receptor involved in learning, memory, and synaptic plasticity--may contribute to the neurologic and cognitive deficits seen in many Lyme disease patients.

Cognitive functioning in late Lyme borreliosis.

Lyme borreliosis, a tick-borne multisystem disease, may cause a variety of neurologic complications, including meningoencephalitis and encephalopathy. To evaluate neurobehavioral function following treated Lyme borreliosis, 15 patients with Lyme disease and complaints of persistent cognitive difficulty a mean of 6.7 months following antibiotic treatment underwent neuropsychological evaluation and were compared with 10 healthy controls, matched in aggregate for age and education, who underwent the identical neuropsychological assessment. Compared with controls, patients with Lyme disease exhibited marked impairment on memory tests and particularly on selective reminding measures of memory retrieval. The memory impairment did not correlate with serum or cerebrospinal fluid anti-Borrelia burgdorferi antibody titers and was not explained by magnetic resonance imaging findings or depression. The cause of this encephalopathy is currently unknown; however, indirect effects of systemic infection or other toxic-metabolic factors may be partly responsible.