Israel Steiner

EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis

Background:  Lyme neuroborreliosis (LNB) is a nervous system infection caused by Borrelia burgdorferi sensu lato (Bb).

The neurotropic herpes viruses: herpes simplex and varicella-zoster

Herpes simplex viruses types 1 and 2 (HSV1 and HSV2) and varicella-zoster virus (VZV) establish latent infection in dorsal root ganglia for the entire life of the host. From this reservoir they can reactivate to cause human morbidity and mortality. Although the viruses vary in the clinical disorders they cause and in their molecular structure, they share several features that affect the course of infection of the human nervous system. HSV1 is the causative agent of encephalitis, corneal blindness, and several disorders of the peripheral nervous system; HSV2 is responsible for meningoencephalitis in neonates and meningitis in adults. Reactivation of VZV, the pathogen of varicella (chickenpox), is associated with herpes zoster (shingles) and central nervous system complications such as myelitis and focal vasculopathies. We review the biological, medical, and neurological aspects of acute, latent, and reactivated infections with the neurotropic herpes viruses.

Mitochondrial neurogastrointestinal encephalomyopathy: an autosomal recessive disorder due to thymidine phosphorylase mutations.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder defined clinically by severe gastrointestinal dysmotility; cachexia; ptosis, ophthalmoparesis, or both; peripheral neuropathy; leukoencephalopathy; and mitochondrial abnormalities. The disease is caused by mutations in the thymidine phosphorylase (TP) gene. TP protein catalyzes phosphorolysis of thymidine to thymine and deoxyribose 1‐phosphate. We identified 21 probands (35 patients) who fulfilled our clinical criteria for MNGIE. MNGIE has clinically homogeneous features but varies in age at onset and rate of progression. Gastrointestinal dysmotility is the most prominent manifestation, with recurrent diarrhea, borborygmi, and intestinal pseudo‐obstruction. Patients usually die in early adulthood (mean, 37.6 years; range, 26–58 years). Cerebral leukodystrophy is characteristic. Mitochondrial DNA (mtDNA) has depletion, multiple deletions, or both. We have identified 16 TP mutations. Homozygous or compound heterozygous mutations were present in all patients tested. Leukocyte TP activity was reduced drastically in all patients tested, 0.009 ± 0.021 μmol/hr/mg (mean ± SD; n = 16), compared with controls, 0.67 ± 0.21 μmol/hr/mg (n = 19). MNGIE is a recognizable clinical syndrome caused by mutations in thymidine phosphorylase. Severe reduction of TP activity in leukocytes is diagnostic. Altered mitochondrial nucleoside and nucleotide pools may impair mtDNA replication, repair, or both. Ann Neurol 2000;47:792–800

Viral encephalitis: a review of diagnostic methods and guidelines for management

Viral encephalitis is a medical emergency. The spectrum of brain involvement and the prognosis are dependent mainly on the specific pathogen and the immunological state of the host. Although specific therapy is limited to only several viral agents, correct immediate diagnosis and introduction of symptomatic and specific therapy has a dramatic influence upon survival and reduces the extent of permanent brain injury in survivors. We searched MEDLINE (National Library of Medicine) for relevant literature from 1966 to May 2004. Review articles and book chapters were also included. Recommendations are based on this literature based on our judgment of the relevance of the references to the subject. Recommendations were reached by consensus. Where there was lack of evidence but consensus was clear we have stated our opinion as good practice points. Diagnosis should be based on medical history, examination followed by analysis of cerebrospinal fluid for protein and glucose contents, cellular analysis and identification of the pathogen by polymerase chain reaction (PCR) amplification (recommendation level A) and serology (recommendation level B). Neuroimaging, preferably by magnetic resonance imaging, is an essential aspect of evaluation (recommendation level B). Lumbar puncture can follow neuroimaging when immediately available, but if this cannot be obtained at the shortest span of time it should be delayed only in the presence of strict contraindications. Brain biopsy should be reserved only for unusual and diagnostically difficult cases. All encephalitis cases must be hospitalized with an access to intensive care units. Supportive therapy is an important basis of management. Specific, evidence‐based, anti‐viral therapy, acyclovir, is available for herpes encephalitis (recommendation level A). Acyclovir might also be effective for varicella‐zoster virus encephalitis, gancyclovir and foscarnet for cytomegalovirus encephalitis and pleconaril for enterovirus encephalitis (IV class of evidence). Corticosteroids as an adjunct treatment for acute viral encephalitis are not generally considered to be effective and their use is controversial. Surgical decompression is indicated for impending uncal herniation or increased intracranial pressure refractory to medical management.

Experimental Allergic Encephalomyelitis: A Misleading Model of Multiple Sclerosis

Despite many years of intensive research, multiple sclerosis (MS) defies understanding and treatment remains suboptimal. The prevailing hypothesis is that MS is immune mediated and that experimental allergic encephalomyelitis (EAE) is a suitable model to elucidate pathogenesis and devise therapy. This review examines critically the validity that EAE is an adequate and useful animal model of MS and finds credible evidence lacking. EAE represents more a model of acute central nervous system inflammation than the counterpart of MS. We propose to reconsider the utilization of EAE, especially when this model is used to define therapy. This will also force us to examine MS without the restraints imposed by EAE, as to what it is, rather than what it looks like. Ann Neurol 2005;58:939–945

Neurologic Aspects of Inflammatory Bowel Disease

Article abstract-To determine the frequency, spectrum, and clinical features of neurologic disorders associated with ulcerative colitis (UC) and Crohns disease (CD). Background: Extraintestinal manifestations of inflammatory bowel disease (IBD) are well documented, but the association of IBD with neurologic involvement is rare and often controversial. Methods: Tertiary care center ambulatory and hospital services data bank retrospective computerized search with subsequent file review. Patients: From among 638 IBD patients diagnosed from 1981 to 1991, we identified 10 CD patients and nine UC patients with neurologic involvement unrelated to a defined systemic or iatrogenic cause. Neurologic disorders diagnosed 15 or more years before the intestinal symptomatology were excluded. Results: Three percent of IBD patients had neurologic involvement. In 14 of 19 (74%), it started within a mean of 5.7 years (range, 0.7 to 12 years) after the diagnosis of bowel disease, and in two of 19 (10%) it occurred at the time of IBD exacerbation. During the course of IBD, 10 of 19 patients (53%) exhibited other extraintestinal manifestations. Peripheral nerve disorders were observed in six UC patients. Myelopathy (5 patients), myopathy (3), and myasthenia gravis (1) were diagnosed in eight CD patients and one UC patient. Cerebrovascular disorders occurred in two UC and two CD patients. Conclusions: Neurologic disorders associated with IBD are more common than appreciated and follow a different pattern of involvement in UC and CD. A prospective study is required to define the nature of this association. NEUROLOGY 1995;45: 416-421

EFNS guideline on the management of community-acquired bacterial meningitis : report of an EFNS Task Force on acute bacterial meningitis in older children and adults

Acute bacterial meningitis (ABM) is a potentially life‐threatening neurological emergency. An agreed protocol for early, evidence‐based and effective management of community‐acquired ABM is essential for best possible outcome. A literature search of peer‐reviewed articles on ABM was used to collect data on the management of ABM in older children and adults. Based on the strength of published evidence, a consensus guideline was developed for initial management, investigations, antibiotics and supportive therapy of community‐acquired ABM. Patients with ABM should be rapidly hospitalized and assessed for consideration of lumbar puncture (LP) if clinically safe. Ideally, patients should have fast‐track brain imaging before LP, but initiation of antibiotic therapy should not be delayed beyond 3 h after first contact of patient with health service. In every case, blood sample must be sent for culture before initiating antibiotic therapy. Laboratory examination of cerebrospinal fluid is the most definitive investigation for ABM and whenever possible, the choice of antibiotics, and the duration of therapy, should be guided by the microbiological diagnosis. Parenteral therapy with a third‐generation cephalosporin is the initial antibiotics of choice in the absence of penicillin allergy and bacterial resistance; amoxicillin should be used in addition if meningitis because of Listeria monocytogenes is suspected. Vancomycin is the preferred antibiotic for penicillin‐resistant pneumococcal meningitis. Dexamethasone should be administered both in adults and in children with or shortly before the first dose of antibiotic in suspected cases of Streptococcus pneumoniae and H. Influenzae meningitis. In patients presenting with rapidly evolving petechial skin rash, antibiotic therapy must be initiated immediately on suspicion of Neisseria meningitidis infection with parenteral benzyl penicillin in the absence of known history of penicillin allergy.

Lyme neuroborreliosis: infection, immunity, and inflammation

Lyme neuroborreliosis (LNB), the neurological manifestation of systemic infection with the complex spirochaete Borrelia burgdorferi, can pose a challenge for practising neurologists. This Review is a summary of clinical presentation, diagnosis, and therapy, as well as of recent advances in our understanding of LNB. Many new insights have been gained through work in experimental models of the disease. An appreciation of the genetic heterogeneity of the causative pathogen has helped clinicians in their understanding of the diverse presentations of LNB.

Viral meningoencephalitis: a review of diagnostic methods and guidelines for management: Viral meningoencephalitis

Background:  Viral encephalitis is a medical emergency. The prognosis depends mainly on the pathogen and host immunologic state. Correct immediate diagnosis and introduction of symptomatic and specific therapy has a dramatic influence upon survival and reduces the extent of permanent brain injury.

The prognostic value of the CT scan in conservatively treated patients with intracerebral hematoma.

Prognostic factors for survival and neurological recovery were assessed in 42 patients with non trauma tic intracerebral hematoma (ICH) diagnosed by CT scan. None underwent surgical evacuation of hematoma. CT scans were used to determine location and volume of ICH and presence or absence of intraventricular hemorrhage (IVH). Only 11 patients (26%) died and 17 patients (40.5%) recovered fully. Mortality was associated with: 1) loss of consciousness as a presenting symptom (63.5% mortality rate versus 13% when there was no loss of consciousness at the onset; (p < 0.01). 2) extension of the bleeding into the ventricular system (45% mortality rate versus 9% when hemorrhages were confined to brain parenchy- ma; (p < 0.01). 3) location of hematoma in the posterior fossa (mortality rate of 43% versus 23% for Intrahemispherlc hematomas). Mortality was unaffected by age of patients and size of ICH. Full neurologi- cal and functional recovery occurred mainly when estimated volume of hematomas was less than 15 cc and with lobar hematomas regardless of size. In survivors there is CT evidence of complete resolution of ICH. Our data indicates a favourable outcome in a relatively large percentage of patients with ICH treated conservatively and therefore questions the need for surgical evacuation of hematoma. Stroke Vol 15, No 1, 1984