Predictors of CNS injury as measured by proton magnetic resonance spectroscopy in the setting of chronic HIV infection and CART.

The reasons for persistent brain dysfunction in chronically HIV-infected persons on stable combined antiretroviral therapies (CART) remain unclear. Host and viral factors along with their interactions were examined in 260 HIV-infected subjects who underwent magnetic resonance spectroscopy (MRS). Metabolite concentrations (NAA/Cr, Cho/Cr, MI/Cr, and Glx/Cr) were measured in the basal ganglia, the frontal white matter, and gray matter, and the best predictive models were selected using a bootstrap-enhanced Akaike information criterion (AIC). Depending on the metabolite and brain region, age, race, HIV RNA concentration, ADC stage, duration of HIV infection, nadir CD4, and/or their interactions were predictive of metabolite concentrations, particularly the basal ganglia NAA/Cr and the mid-frontal NAA/Cr and Glx/Cr, whereas current CD4 and the CPE index rarely or did not predict these changes. These results show for the first time that host and viral factors related to both current and past HIV status contribute to persisting cerebral metabolite abnormalities and provide a framework for further understanding neurological injury in the setting of chronic and stable disease.

Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To assess the evidence for the efficacy of IV immunoglobulin (IVIg) to treat neuromuscular disorders. METHODS: The MEDLINE, Web of Science, and EMBASE databases were searched (1966-2009). Selected articles were rated according to the American Academy of Neurology's therapeutic classification of evidence scheme; recommendations were based on the evidence level. RESULTS AND RECOMMENDATIONS: IVIg is as efficacious as plasmapheresis and should be offered for treating Guillain-Barré syndrome (GBS) in adults (Level A). IVIg is effective and should be offered in the long-term treatment of chronic inflammatory demyelinating polyneuropathy (Level A). IVIg is probably effective and should be considered for treating moderate to severe myasthenia gravis and multifocal motor neuropathy (Level B). IVIg is possibly effective and may be considered for treating nonresponsive dermatomyositis in adults and Lambert-Eaton myasthenic syndrome (Level C). Evidence is insufficient to support or refute use of IVIg in the treatment of immunoglobulin M paraprotein-associated neuropathy, inclusion body myositis, polymyositis, diabetic radiculoplexoneuropathy, or Miller Fisher syndrome, or in the routine treatment of postpolio syndrome or in children with GBS (Level U). IVIg combined with plasmapheresis should not be considered for treating GBS (Level B). More data are needed regarding IVIg efficacy as compared with other treatments/treatment combinations. Most studies concluded IVIg-related serious adverse effects were rare. Given the variable nature of these diseases, individualized treatments depending on patient need and physician judgment are important.

Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To reassess the role of plasmapheresis in the treatment of neurologic disorders. METHODS: We evaluated the available evidence based on a structured literature review for relevant articles from 1995 through September 2009. In addition, due to revision of the definitions of classification of evidence since the publication of the previous American Academy of Neurology assessment in 1996, the evidence cited in that manuscript was reviewed and reclassified. RESULTS AND RECOMMENDATIONS: Plasmapheresis is established as effective and should be offered in severe acute inflammatory demyelinating polyneuropathy (AIDP)/Guillain-Barré syndrome (GBS) and in the short-term management of chronic inflammatory demyelinating polyneuropathy (Class I studies, Level A). Plasmapheresis is established as ineffective and should not be offered for chronic or secondary progressive multiple sclerosis (MS) (Class I studies, Level A). Plasmapheresis is probably effective and should be considered for mild AIDP/GBS, as second-line treatment of steroid-resistant exacerbations in relapsing forms of MS, and for neuropathy associated with immunoglobulin A or immunoglobulin G gammopathy, based on at least one Class I or 2 Class II studies (Level B). Plasmapheresis is probably not effective and should not be considered for neuropathy associated with immunoglobulin M gammopathy, based on one Class I study (Level B). Plasmapheresis is possibly effective and may be considered for acute fulminant demyelinating CNS disease (Level C). There is insufficient evidence to support or refute the use of plasmapheresis for myasthenia gravis, pediatric autoimmune neuropsychiatric disorders associated with streptococcus infection, and Sydenham chorea (Class III evidence, Level U).

The relation of low glycaemic index fruit consumption to glycaemic control and risk factors for coronary heart disease in type 2 diabetes.

AIMS/HYPOTHESIS: Sugar has been suggested to promote obesity, diabetes and coronary heart disease (CHD), yet fruit, despite containing sugars, may also have a low glycaemic index (GI) and all fruits are generally recommended for good health. We therefore assessed the effect of fruit with special emphasis on low GI fruit intake in type 2 diabetes. METHODS: This secondary analysis involved 152 type 2 diabetic participants treated with glucose-lowering agents who completed either 6 months of high fibre or low GI dietary advice, including fruit advice, in a parallel design. RESULTS: Change in low GI fruit intake ranged from -3.1 to 2.7 servings/day. The increase in low GI fruit intake significantly predicted reductions in HbA(1c) (r = -0.206, p =0.011), systolic blood pressure (r = -0.183, p = 0.024) and CHD risk (r = -0.213, p = 0.008). Change in total fruit intake ranged from -3.7 to 3.2 servings/day and was not related to study outcomes. In a regression analysis including the eight major carbohydrate foods or classes of foods emphasised in the low GI diet, only low GI fruit and bread contributed independently and significantly to predicting change in HbA(1c). Furthermore, comparing the highest with the lowest quartile of low GI fruit intake, the percentage change in HbA(1c) was reduced by -0.5% HbA(1c) units (95% CI 0.2-0.8 HbA(1c) units, p < 0.001). CONCLUSIONS/INTERPRETATION: Low GI fruit consumption as part of a low GI diet was associated with lower HbA(1c), blood pressure and CHD risk and supports a role for low GI fruit consumption in the management of type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00438698.

Bilateral isolated phrenic neuropathy causing painless bilateral diaphragmatic paralysis.

The authors report four patients with a syndrome of painless bilateral isolated phrenic neuropathy. Electrophysiologic testing demonstrated active denervation restricted to the diaphragm. Long-term recovery was poor. The authors conclude that bilateral isolated phrenic neuropathy is a cause of painless diaphragmatic paralysis distinguishable from immune brachial plexus neuropathy and other neuromuscular disorders with similar clinical presentation.

Quantitative sensory testing: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: This assessment evaluates the clinical utility, efficacy, and safety of quantitative sensory testing (QST). METHODS: By searching MEDLINE, Current Contents, and their personal files, the authors identified 350 articles. Selected articles utilized computer operated threshold systems, manually operated threshold systems, and electrical threshold devices. The authors evaluated the use of normal values and the degree of reproducibility between the same and different systems. Articles were rated using a standard classification of evidence scheme. RESULTS: Because of differences between systems, normal values from one system cannot be transposed to others. Reproducibility of results was also an important concern, and there is no consensus on how it should be defined. The authors identified no adequately powered class I studies demonstrating the effectiveness of QST in evaluating any particular disorder. A number of class II and III studies demonstrated that QST is probably or possibly useful in identifying small or large fiber sensory abnormalities in patients with diabetic neuropathy, small fiber neuropathies, uremic neuropathies, and demyelinating neuropathy. CONCLUSIONS: QST is a potentially useful tool for measuring sensory impairment for clinical and research studies. However, QST results should not be the sole criteria used to diagnose pathology. Because malingering and other nonorganic factors can influence the test results, QST is not currently useful for the purpose of resolving medicolegal matters. Well-designed studies comparing different QST devices and methodologies are needed and should include patients with abnormalities detected solely by QST.

Rippling muscle disease: evidence for phenotypic and genetic heterogeneity.

We describe the clinical features of a family with rippling muscle disease. Muscle stiffness and myalgia were the most prominent symptoms. Muscle rippling, although distinctive, was present in only 6 of the 11 affected family members, whereas persistent muscle contraction to muscle percussion was present in all affected adults. Although this persistent contraction resembled percussion myotonia, it was electrically silent and is therefore more aptly called "percussion contracture." We also observed two clinical features not emphasized in previously reported kindreds: mild but asymptomatic weakness of face or proximal muscles was present in 5 of 11 affected members, and 5 individuals also complained of toe walking after a prolonged period of inactivity, reflecting the disproportionate involvement of the calf muscles. The pedigree suggested autosomal dominant inheritance. Our linkage analysis excluded the region on chromosome 1q identified in a previous linkage study.

Sensory nerve conduction study of the mental nerve.

We describe a technique for sensory nerve conduction study of the mental nerve. A monopolar recording needle is placed near the mandibular foramen using the same approach as that for routine inferior alveolar nerve block in dentistry, and a surface reference electrode is positioned over the ipsilateral mastoid process. Sensory nerve action potentials to stimulation of the mental nerve at the chin can be reliably recorded orthodromically in normal healthy subjects. The method is simple and well tolerated and provides a useful means to evaluate mental nerve function electrophysiologically.

Electrodiagnostic features of hereditary neuropathy with liability to pressure palsies.

OBJECTIVE: Because diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP) frequently is missed or delayed, we looked for electrodiagnostic features that raise suspicion of the disorder by making comparisons with two more common diseases that mimic it electrophysiologically: chronic inflammatory demyelinating polyneuropathy (CIDP) and diabetic polyneuropathy. METHODS: A retrospective review of the neuromuscular laboratory database was performed. RESULTS: Nine HNPP subjects, 22 with CIDP and 49 with diabetic polyneuropathy. Of all the HNPP nerves studied, abnormally slow sensory nerve conduction velocity (SNCV) was found in 93%, prolonged distal motor latencies (DML) in 78%, slow motor nerve conduction velocity in 31%, and prolonged F-wave latencies in 90%. Mean SNCV for HNPP was 85.6%+/-10.6% of the lower limit of normal and significantly slower than for CIDP (114.3%+/-20.1%; p<0.0001) or diabetes (108.1%+/-14.8%; p<0.0001). Excluding the carpal tunnel site from the analysis did not alter this observation: Mean DML were more prolonged in HNPP, even without median nerve data in the analysis (118.5%+/-31.0% of the upper limit of normal), than in CIDP (103.2%+/-31.6%; p<0.05) or diabetes (86.3%+/-18.3%; p<0.0001). Mean HNPP motor nerve conduction velocity was within normal limits. CONCLUSIONS: According to findings, hereditary neuropathy with liability to pressure palsies (HNPP) has a distinctive background polyneuropathy independent of superimposed entrapment neuropathy. It is characterized by diffuse sensory nerve conduction velocity (SNCV) slowing and prolongation of distal motor latencies with relatively infrequent and minor reduction of motor nerve conduction velocities. This indicates disproportionate distal conduction slowing in the disorder.

Sciatic neuropathy.

Injuries to the sciatic nerve cause neurologic deficits in the peroneal and tibial nerve distributions. Interestingly, most injuries result in more severe deficits to the peroneal division compared to the tibial division. Thus, it can sometimes be difficult to distinguish sciatic neuropathy from peroneal neuropathy. The long course of the sciatic nerve leaves it vulnerable to nerve injury from a variety of causes. Most sciatic neuropathies are acute in onset, such as from hip arthroplasty and hip fracture or dislocation, but some occur from prolonged compression, such as during coma. Entrapment of the sciatic nerve by mass lesions or by the piriformis muscle is relatively rare.

Guidelines in electrodiagnostic medicine. Practice parameter for needle electromyographic evaluation of patients with suspected cervical radiculopathy.

Cervical radiculopathy is a common cause of morbidity. Its management often requires clinical, electrodiagnostic, and radiological evaluation, and its treatment may include surgery. Based on a critical review of the literature, electrodiagnostic evaluation is found to be moderately sensitive and highly specific in establishing a diagnosis of cervical radiculopathy. This document defines teh guidelines and options for the electrodiagnostic medicine consultation of patients with suspected cervical radiculopathy.

The electrophysiologic features of sciatic neuropathy in 100 patients.

We reviewed the electrophysiologic data of 100 consecutive patients with sciatic neuropathy in order to better understand this disorder. Most patients (93%) had electrodiagnostic signs of significant axonal loss. Seven patients had predominantly signs of demyelination; 6 were due to compression and 1 was idiopathic. The peroneal division was more severely affected than the tibial division in 64% of patients. Tibialis anterior EMGs were abnormal in 92%, and the EDB CMAP was low in amplitude or absent in 80%. CMAP and SNAP amplitudes and EMGs were all normal in the tibial division in 12%. In contrast, the tibial division was more severely affected in only 8 patients. Of those, 5 were due to thigh trauma (gunshot wounds or femur fracture), 2 from gunshot wounds to the hip, and the other was chronic and idiopathic. Sciatic neuropathies are commonly, but not always, axonal loss lesions that affect the peroneal greater than tibial division.

Sciatic neuropathy: clinical and prognostic features in 73 patients.

We examined the clinical features of patients with sciatic neuropathy and the factors that influence prognosis. Of 92 consecutive patients referred for EMG evaluation of sciatic neuropathy, 73 fulfilled strict inclusion and exclusion criteria and had adequate clinical and electrophysiologic information. The etiologies included hip arthroplasty (21.9%), acute external compression (13.7%), infarction (9.6%), gunshot wound (9.6%), hip fracture/dislocation (9.6%), femur fracture (4.1%), contusion (4.1%), and uncertain (16.4%). We used life table analysis to determine outcome and to identify prognostic factors in patients with acute or subacute onset. Moderate or better recovery (improvement to grade 2 or by two of six clinical grades) occurred in most patients (30% by 1 year, 50% by 2 years, 75% by 3 years). A subgroup experienced excellent improvement (by three of six grades, or to grade 2) less frequently (33% by 2 and 3 years). Of the nine factors tested, two predicted an earlier or better recovery: a recordable compound muscle action potential of the extensor digitorum brevis (p < 0.025), and an initial absence of paralysis of muscles controlling ankle plantar flexion and dorsiflexion (p < 0.05). Thus, good but incomplete recovery occurs over 2 to 3 years in most patients with sciatic neuropathy, particularly in those without severe motor axonal loss.

Deep prepiriform cortex modulates kainate-induced hippocampal injury.

As seizure propagation within limbic structures is mediated in part by a small area of deep prepiriform cortex (area tempestas), we investigated the role of area tempestas in modulating hippocampal injury induced by systemic kainate administration. Injury was quantitated by counting the numbers of neurons that stained for the 72,000 mol. wt heat shock protein and with acid-fuchsin dye. Status epilepticus induced these markers of neuronal injury in the CA1 and CA3a regions of the hippocampus, thalamus, piriform cortex and the amygdaloid complex. Microinjection of 2-amino-7-phosphonoheptanoic acid, a competitive antagonist of the N-methyl-D-aspartate subclass of the glutamate receptor, into area tempestas prior to systemic administration of kainate attenuated both heat shock protein induction and acid-fuchsin labeling in CA1 and CA3a pyramidal neurons without reducing the duration of electrographic seizures. Injections of bicuculline, a GABA antagonist, into area tempestas produced hippocampal damage when given with subcytotoxic doses of intravenous kainate. Thus, area tempestas may be a uniquely sensitive anatomical structure involved not just in seizure propagation but also in modulating the extent and pattern of damage induced in hippocampal neurons as a result of prolonged, systemically induced seizures. These effects are due in part to excitatory and inhibitory projections to neurons in area tempestas.

Acute lumbosacral polyradiculopathy in acquired immunodeficiency syndrome: experience in 23 patients.

We reviewed our experience in 23 patients with acquired immunodeficiency syndrome (AIDS) who had acute lumbosacral polyradiculopathy. The patients developed a distinctive syndrome of rapidly progressive flaccid paraparesis and areflexia that was frequently associated with sphincter disturbances. Persuasive laboratory evidence of a cytomegalovirus polyradiculopathy (polymorphonuclear pleocytosis or confirmatory cerebrospinal fluid culture) was found in 15 of the 23 patients. Treatment with ganciclovir in these patients led to clinical stabilization, although worsening during the first 2 weeks of treatment was common. Most patients with cytomegalovirus polyradiculopathy had severe residual deficits. Metastasis from systemic lymphoma accounted for the polyradiculopathy in 2 other patients. A more benign syndrome was identified in the remaining 6 patients. They generally had slower clinical progression and less severe neurological deficits at their nadir than did patients with cytomegalovirus polyradiculopathy. Unlike patients with cytomegalovirus infection, their cerebrospinal fluid showed a predominantly mononuclear pleocytosis. Moreover, spontaneous improvement without treatment was common. Our experience together with the published experience of others suggests that the acute lumbosacral polyradiculopathy in AIDS is a clinical syndrome with different etiologies and variable clinical outcome. Recognition of this heterogeneity is necessary for the management of individual patients, as well as the interpretation of treatment results.

Literature review of the usefulness of nerve conduction studies and electromyography for the evaluation of patients with carpal tunnel syndrome. AAEM Quality Assurance Committee.

The sensitivity and specificity of nerve conduction studies (NCS's) and electromyography (EMG) for the diagnosis of carpal tunnel syndrome (CTS) were evaluated by a critical review of the literature. With a search of the medical literature in English through May 1991, 165 articles were identified and reviewed on the basis of six criteria of scientific methodology. The findings of 11 articles that met all six criteria and the results of 48 additional studies that met four or five criteria are presented. We concluded that median sensory and motor NCS's are valid and reproducible clinical laboratory studies that confirm a clinical diagnosis of CTS with a high degree of sensitivity and specificity. Clinical practice recommendations are made based on a comparison of the sensitivities of the several different median nerve conduction study (NCS) techniques.

Clinical and radiographic findings in disseminated tuberculosis of the brain.

We report clinical and radiographic findings in a patient with disseminated tuberculosis (TB) of the brain. A Burmese man developed a left hemiparesis and mild cognitive difficulty 1 month into therapy for miliary TB. A head MRI showed numerous (> 100) contrast-enhancing supratentorial and infratentorial lesions. Following 9 months of treatment with isoniazid, ethambutol, rifampin, and pyrazinamide, most lesions resolved; however, one cortical tuberculoma enlarged significantly. The patient was continued on isoniazid and rifampin, with radiographic resolution of the tuberculoma 4 months later.

Distribution of HSP72 induction and neuronal death following limbic seizures.

A small area of deep prepiriform cortex is uniquely susceptible to convulsant and anticonvulsant drugs in the rat. We have studied the pattern of expression of the non-constitutive stress protein (HSP72) following seizures induced by unilateral microinjection of bicuculline into this area. HSP was seen first in ipsilateral dorsal medial thalamus, amygdala and associated piriform cortex, and with more sustained seizures was seen bilaterally in these structures as well as in other projection sites. Neuronal cell death, as assessed by acid-fuchsin staining, occurred in the same brain regions. Frank necrosis was found in the ipsilateral piriform cortex with prolonged seizures. Behaviorally, the seizures induced are characteristic of involvement of the limbic system and, therefore, may be a model of human complex partial seizures.

AAEM case report #23: acute paralytic poliomyelitis.

A 56-year-old man with acute paralytic poliomyelitis is described. The illness started with fever and diarrhea after an overseas trip, and an enterovirus other than poliovirus was isolated from the patient's stool. The onset of weakness was rapid and asymmetric, with primary involvement of the lower extremities. Nerve conduction studies revealed low amplitude motor responses after the first week, with normal results for sensory studies. Serial electromyographic studies were performed, documenting acute denervation followed later by reinnervation in the distribution of multiple segments. The clinical and electrodiagnostic features of acute poliomyelitis are reviewed.