Search

Dominant intermediate Charcot-Marie-Tooth neuropathy subtype C (DI-CMTC) was associated with mutations in the YARS gene, encoding tyrosyl-tRNA synthetase, in two large unrelated Bulgarian and US pedigrees and one sporadic case. Here for the first time we describe the clinical, neurophysiological and histopathological features, and phenotypic differences between these two DI-CMTC families. Twenty-one affected individuals from the US family and 27 from the Bulgarian family were evaluated. The mean age of onset in US subjects was 10.7 years in men and 7.3 years in women, while in the Bulgarian participants it was 18.2 years in men and 33.7 years in women. The course was slowly progressive. Extensor digitorum brevis atrophy was uniform. Atrophy and/or weakness of upper and lower limb muscles were found in over 50 % of the subjects. Nerve conduction studies (NCS) were abnormal in all US adults and five of six children and all Bulgarian patients except one asymptomatic 25-year-old man. Median motor NCS were in the range of 29.545.6 m/s in the US family and 24.757.8 m/s in the Bulgarian family. Sural sensory nerve action potentials were absent in 14/21 and 4/12 NCS from adult US and Bulgarian participants, respectively. Analysis of sural nerve biopsies from US patients revealed age-dependent morphological changes of axonal degeneration, absence of onion bulbs, and

How many of us in clinical practice have heard the question: “Doctor, will this drug interact with any of my other medications?” This common question has been challenging to answer, often leading to using laborious drug interaction computer programs, smartphone-based programs, or a call to the pharmacist. The purpose of this chapter is to help address this question, assess the likelihood of a drug-drug interaction, and advise the patient on what to expect should they experience an adverse drug effect.

Neurologists frequently encounter patients with psychiatric conditions, either primary or as a complication of neurologic disease. All neurologists see patients with mood disorders, and many are comfortable prescribing a first-line agent such as an SSRI. In fact, a majority of mood disorders are treated by non-psychiatrists. Newer data shows the high prevalence of mood disorders in neurologic disease, such as Parkinson disease, stroke, and dementia. Depression occurs in a third of survivors of stroke and is associated with higher mortality. Depression has also been noted to increase the likelihood of later dementia.

Head injury has been recognized as an increasingly important determinant of late-life cognitive function. Despite a large number of research and clinical studies, no direct link has been established between minor head trauma with or without loss of consciousness and the development of dementia of the Alzheimer type. Similarly for alcohol, low doses have been found to be somewhat protective against dementia, whereas large doses increased the risk of late-life cognitive dysfunction. Among the many environmental toxins suspected of causing cognitive dysfunction, lead intoxication has the strongest evidence to support a link.

Background Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of laboratory and genetic tests for the assessment of DSP. Methods A literature review using MEDLINE, EMBASE, Science Citation Index and Current Contents was performed to identify the best evidence regarding the evaluation of polyneuropathy published between 1980 and March 2007. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based upon the level of evidence. Results and Conclusions 1. Screening laboratory tests may be considered for all patients with polyneuropathy (Level C). Those tests that provide the highest yield of abnormality are blood glucose, serum B12 with metabolites (methylmalonic acid with or without homocysteine) and serum protein immunofixation electrophoresis (Level C). If there is no definite evidence of diabetes mellitus by routine testing of blood glucose, testing for impaired glucose tolerance may be considered in distal symmetric sensory polyneuropathy (Level C). 2. Genetic testing is established as useful for the accurate diagnosis and classification of hereditary neuropathies (Level A). Genetic testing may be considered in patients with cryptogenic polyneuropathy who exhibit a hereditary neuropathy phenotype (Level C). Initial genetic testing should be guided by the clinical phenotype, inheritance pattern, and electrodiagnostic (EDX) features and should focus on the most common abnormalities which are CMT1A duplication/HNPP deletion, Cx32 (GJB1 ), and MFN2 mutation screening. There is insufficient evidence to determine the usefulness of routine genetic testing in patients with cryptogenic polyneuropathy who do not exhibit a hereditary neuropathy phenotype (Level U).

Background: Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of autonomic testing, nerve biopsy, and skin biopsy for the assessment of polyneuropathy.Methods: A literature review using MEDLINE, EMBASE, and Current Contents was performed to identify the best evidence regarding the evaluation of polyneuropathy published between 1980 and March 2007. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based upon the level of evidence.Results and Recommendations: 1) Autonomic testing should be considered in the evaluation of patients with polyneuropathy to document autonomic nervous system dysfunction (Level B). Such testing should be considered especially for the evaluation of suspected autonomic neuropathy (Level B) and distal small fiber sensory polyneuropathy (SFSN) (Level C). A battery of validated tests is recommended to achieve the highest diagnostic accuracy (Level B). 2) Nerve biopsy is generally accepted as useful in the evaluation of certain neuropathies as in patients with suspected amyloid neuropathy, mononeuropathy multiplex due to vasculitis, or with atypical forms of chronic inflammatory demyelinating polyneuropathy (CIDP). However, the literature is insufficient to provide a recommendation regarding when a nerve biopsy may be useful in the evaluation of DSP (Level U). 3) Skin biopsy is a validated technique for determining intraepidermal nerve fiber density and may be considered for the diagnosis of DSP, particularly SFSN (Level C). There is a need for additional prospective studies to define more exact guidelines for the evaluation of polyneuropathy.AAN = American Academy of Neurology; AANEM = American Academy of Neuromuscular and Electrodiagnostic Medicine; AAPM&R = American Academy of Physical Medicine and Rehabilitation; ART = autonomic reflex testing; BRSI = baroreflex sensitivity index; CASS = composite autonomic scoring scale; CIDP = chronic inflammatory demyelinating polyneuropathy; DSFN = distal small fiber neuropathy; DSP = distal symmetric polyneuropathy; EDx = electrodiagnosis; EFNS = European Federation of Neurological Societies; HRV = heart rate variability; IAN = idiopathic autonomic neuropathy; IENF = intraepidermal nerve fibers; MSNA = muscle sympathetic nerve activity; NCSs = nerve conduction studies; PGP 9.5 = protein-gene-product 9.5; PN = peripheral neuropathy; PRT = blood pressure recovery time; QAE = quantitative autonomic examination; QSART = quantitative sudomotor axon reflex test; QSS = Quality Standards Subcommittee; QST = quantitative sensory testing; SFSN = small fiber sensory polyneuropathy; TST = thermoregulatory sweat testing.

Objective: To describe the clinical and laboratory features of a painful non-length dependent, small fibre ganglionopathy (SFG). Background: The syndrome of generalised SFG with early involvement of the face, trunk or proximal limbs is not well recognised and contrasts with the burning feet syndrome of small fibre neuropathy (SFN) and classical large fibre features of sensory ganglionopathy. Methods: Retrospective case review including skin biopsies from four neuromuscular centres. Patients with pre-existing diseases associated with ganglionopathies were excluded. Results: 12 men and 11 women, with an average age of 50 years, were studied. Neuropathic pain developed over days in eight and over months in the other patients. The face (n = 12), scalp (n = 10), tongue (n = 6), trunk (n = 15) and acral extremities (n = 21) were involved. Symptoms began in the hands or face before the legs in 10. The pain was characterised as burning (n = 22), prickling (n = 13), shooting (n = 13) or allodynic (n = 11). There was loss of pinprick sensation in affected regions in 19, with minimal or no loss of large fibre sensibility. Laboratory findings included abnormal glucose metabolism in six patients, Sjogren syndrome in three and monoclonal gammopathy, sprue and hepatitis C infection in one each, with the remainder idiopathic. Sensory nerve action potentials were normal in 12 and were reduced in the hands but normal in the legs in six. Skin biopsy in 14 of 17 showed reduced nerve fibre density in the thigh equal to or more prominent than in the calf. Two of seven patients improved with immune therapies, 13 symptomatically with analgesic medications and the remainder had little improvement. Ten considered the pain disabling at the last follow-up (mean 2 years). Conclusion: The pattern of symmetric, non-length dependent neuropathic pain with face and trunk involvement suggests a selective disorder of the dorsal ganglia cells subserving small nerve fibres. It can be distinguished from distal SFN. A potential metabolic or immune process was detected in half of the cases and the disorder was often refractory to treatment.

Tibial mononeuropathies most commonly occur at the popliteal fossa or tarsal tunnel. We present an unusual case of nontraumatic tibial neuropathy of uncertain etiology occurring in the mid lower leg. External neurolysis resulted in an excellent recovery.

Dysautonomias are a heterogeneous group of disorders with pathologic changes confined to the central nervous system, the peripheral nervous system or both, depending on the underlying condition [1–3]. Autonomic dysfunction, including postural tachycardia syndrome (POTS), Parkinson’s disease, multiple system atrophy and autonomic neuropathies are major public health problems with a large unmet clinical need [4, 5]. However, advances in therapies that have an immediate impact on quality of life and outcomes in patients with autonomic disorders have been limited. Due to the limitations of many treatment options, particularly in disorders such as POTS, novel treatments have been considered. Into this therapeutic void a therapy for modulation of autonomic function is being advocated as a clinical treatment for autonomic dysfunction of all types. This therapy, described as transvascular autonomic modulation, utilizes an endovascular approach to dilate the thoracic venous system, resulting in mechanical stretching of the autonomic nerves and ‘resetting’ of the autonomic nervous system. The scientific rationale for this procedure is not well described, nor does there appear to be any clear evidence supporting the use of this technique in a diverse group of autonomic disorders. This method reports mechanical disruption of baroreceptors in the venous system using transvenous balloon inflation as a method to improve autonomic dysfunction. There are several major scientific concerns with this statement. First, there is no evidence of such venous baroreceptors. Second, patients with Parkinson’s disease have progressive autonomic nerve fiber dysfunction due to axon loss. There is no evidence, practical or theoretical, to suggest that inflating a balloon in a vein would halt or reverse the loss of nerve fibers secondary to alpha-synuclein deposition in a progressive neurodegenerative condition [6–8]. Promoting a single therapy to treat a group of diseases such as multiple sclerosis, postural tachycardia syndrome and Parkinson’s disease suggests a serious deviation from scientific understanding of disease pathophysiology [9]. We performed an exhaustive review of all available literature describing this procedure through a search of Pubmed and Google Scholar (covering articles published from 1 January 1970 to 9 January 2013). We did not find a single published report describing this procedure. A number of reports have been published describing a similar procedure that has been proposed for the treatment of chronic cerebrospinal venous insufficiency. Originally developed as a possible treatment for multiple sclerosis, this therapeutic approach currently has a negative FDA advisory statement because of complications that include stroke, blood clots, nerve damage and death [10]. We strongly encourage the development of novel approaches and therapeutic interventions for dysautonomia, but only when they are based on scientific rationale and supported by evidence of both safety and efficacy. At this stage, there are no data at all to support the clinical utility of transvascular autonomic modulation and there is no scientific rationale for the procedure. Until randomized blinded trials are completed to ensure adequate understanding of safety and efficacy, we cannot recommend transvascular modulation, or any other unproven surgical procedure, as a treatment for autonomic dysfunction.

Intellectual satisfaction derived from making a correct diagnosis is heightened by the knowledge that treatment, free of side effects, can prevent further progression of disease and may even reverse some or all of the disease manifestations. The paradigm for this situation in neurology has been the disease pernicious anemia (PA), with its associated deficiency of cobalamin (Cbl) leading, if untreated, to progressive spinal cord degeneration, neuropathy, and cerebral complications. There was a time when an astute clinician might have considered that the diagnosis of PA or other causes of Cbl deficiency was relatively simple and treatment straightfor-ward. A patient experiencing neurologic complaints, often affecting sensory and motor function in the lower extremities, would have been found to have macrocytic anemia. To confirm the suspicion, the patient might have had a smooth tongue, prematurely graying hair, lemon-yellow skin, and a family history of anemia requiring monthly ``vitamin shots.'' The diagnosis would have been confirmed by a serum Cbl determination followed by treatment with vitamin cyanocobalamin (vitamin B12; B12). Despite, or perhaps because of, a number of advances in our understanding of Cbl metabolism, we more frequently encounter patients with unusual or atypical clinical and laboratory features who have underlying Cbl deficiency. Subacute combined degeneration of the spinal cord, neuropathy, and other classic manifestations of Cbl deficiency in the nervous system are often easy to recognize, but we now know that there are many atypical presentations. [1-4] Some patients have neurologic syndromes without anemia or macrocytosis, whereas others have a normal serum Cbl level, yet are found to have other biochemical evidence of Cbl deficiency such as raised levels of the metabolites methylmalonic acid and homocysteine. Appropriate investigation is critical, because early treatment affords the possibility of excellent recovery. What are the reasons for this seeming change from …

Objective: To elucidate the usefulness of clinical orthostatic blood pressure testing (COBP) as a screening tool for autonomic dysfunction. Study Design: In this retrospective case review, the records of 156 consecutive patients with nonotologic dizziness as the primary complaint seen in an academic neurotology clinic between 2005 and 2009 were reviewed. The objective of this study was accomplished by comparing the diagnostic yield of COBP with that of head-upright tilt table testing (HUT) and assessing the sensitivity and specificity of COBP in predicting an abnormal HUT in patients with nonotologic dizziness. Setting: Ambulatory tertiary referral center. Patients: Patients presenting to the clinic with dizziness without otologic cause. Intervention(s): Clinical evaluation, orthostatic blood pressure testing, and HUT. Main Outcome Measure(s): The primary outcome assessed in this study was patient blood pressure. Blood pressures were measured in the clinic in the following order: supine, sitting, and standing. Positive COBP was defined as a reduction in systolic or diastolic blood pressure greater than 20 or 10 mm Hg, respectively, or both, within 3 minutes of sitting from supine or standing from sitting. For comparison, HUT was used as the gold standard. A positive HUT was defined as a reduction in systolic or diastolic blood pressure greater than 20 or 10 mm Hg, respectively, or both, relative to baseline at any point after initiation of HUT. Results: Forty patients were referred for HUT. Twenty-four (61.5%) of these patients were deemed to have a positive response. Thirty-three patients (85%) referred to HUT were initially evaluated with COBP, which revealed orthostatic hypotension (OH) in 8 patients (24%). COBP was calculated to have sensitivity and specificity of 21% and 71%, respectively, when asymptomatic OH was included in the positivity criteria. When asymptomatic OH was excluded from the positivity criteria, the sensitivity and specificity remained similar at 25% and 76%, respectively. However, the exclusion of asymptomatic OH from the positivity criteria resulted in a decrease in the positive predictive value from 50% to 25% and an increase in the negative predictive value from 40% to 76%. Overall, HUT detected 16 patients with an abnormal result that were missed by COBP testing. Conclusion: Evaluation for autonomic dysfunction should be part of the comprehensive evaluation of a dizzy patient, involving, at a minimum, orthostatic testing of blood pressure and heart rate. Patients with nonotologic dizziness and light-headedness with a normal neurotologic evaluation can reasonably be referred for HUT, even in the presence of normal in-office orthostatic testing.

Objective The aim of this study was to evaluate the efficacy of a therapeutic pathway for vestibular migraine (VM) and complex dizziness of undetermined etiology (CDUE) with caffeine cessation and pharmacotherapy. Study Design This study is a retrospective chart review. Intervention(s) Patients were recommended to stop intake of caffeine and other putative migraine-triggering agents. Pharmacotherapy was initiated with nortriptyline or topiramate if symptoms persisted despite diet modification. Main Outcome Measure Self-reported dizziness is the main outcome measure. Results Vestibular migraine and CDUE were considered contributing factors to dizziness in 34 and 10, respectively, of 156 patients. Fourteen percent of patients reported improvement in symptoms upon caffeine cessation, whereas 46% of patients reported a reduction in dizziness after nortriptyline therapy ( P = .007). Topiramate reduced symptoms in 25% of patients. In total, 75% of VM patients and 56% of patients with CDUE received sufficient benefit from this therapeutic pathway to not progress to other treatments. Conclusions Vestibular migraine and CDUE can be treated effectively with a therapeutic pathway consisting of caffeine cessation followed by pharmacotherapy.

The impact of transcranial Doppler ultrasound (TCD) on the management of 107 consecutively referred patients with suspected vertebrobasilar ischemia was studied. Physicians who referred patients for TCD of the posterior circulation were interviewed before and after being given the results of the TCD examination. Management plans devised prior to knowledge of the TCD results were compared to those devised after TCD results were given. Management changed in 42% of the patients after TCD results were given, and there was a 58% reduction in the use of angiography (p = 0.04) and a 128% increase in the use of aspirin (p = 0.005). Changes in the use of anticoagulants and other diagnostic or therapeutic approaches were not significant. TCD appears to have a significant impact on the management of patients with suspected vertebrobasilar ischemia.

Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of autonomic testing, nerve biopsy, and skin biopsy for the assessment of polyneuropathy. A literature review using MEDLINE, EMBASE, Science Citation Index, and Current Contents was performed to identify the best evidence regarding the evaluation of polyneuropathy published between 1980 and March 2007. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based on the level of evidence. (1) Autonomic testing may be considered in the evaluation of patients with polyneuropathy to document autonomic nervous system dysfunction (Level B). Such testing should be considered especially for the evaluation of suspected autonomic neuropathy (Level B) and distal small fiber sensory polyneuropathy (SFSN) (Level C). A battery of validated tests is recommended to achieve the highest diagnostic accuracy (Level B). (2) Nerve biopsy is generally accepted as useful in the evaluation of certain neuropathies as in patients with suspected amyloid neuropathy, mononeuropathy multiplex due to vasculitis, or with atypical forms of chronic inflammatory demyelinating polyneuropathy (CIDP). However, the literature is insufficient to provide a recommendation regarding when a nerve biopsy may be useful in the evaluation of DSP (Level U). (3) Skin biopsy is a validated technique for determining intraepidermal nerve fiber (IENF) density and may be considered for the diagnosis of DSP, particularly SFSN (Level C). There is a need for additional prospective studies to define more exact guidelines for the evaluation of polyneuropathy.

Background:Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of laboratory and genetic tests for the assessment of DSP.Methods:A literature review using MEDLINE, EMBASE, and Current Contents was performed to identify the best evidence regarding the evaluation of polyneuropathy published between 1980 and March 2007. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based upon the level of evidence.Results and Recommendations:1) Screening laboratory tests may be considered for all patients with polyneuropathy (Level C). Those tests that provide the highest yield of abnormality are blood glucose, serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein immunofixation electrophoresis (Level C). If there is no definite evidence of diabetes mellitus by routine testing of blood glucose, testing for impaired glucose tolerance may be considered in distal symmetric sensory polyneuropathy (Level C). 2) Genetic testing should be conducted for the accurate diagnosis and classification of hereditary neuropathies (Level A). Genetic testing may be considered in patients with cryptogenic polyneuropathy who exhibit a hereditary neuropathy phenotype (Level C). Initial genetic testing should be guided by the clinical phenotype, inheritance pattern, and electrodiagnostic features and should focus on the most common abnormalities which are CMT1A duplication/HNPP deletion, Cx32 (GJB1), and MFN2 mutation screening. There is insufficient evidence to determine the usefulness of routine genetic testing in patients with cryptogenic polyneuropathy who do not exhibit a hereditary neuropathy phenotype (Level U).AAN= American Academy of Neurology;AANEM= American Academy of Neuromuscular and Electrodiagnostic Medicine;AAPM&R= American Academy of Physical Medicine and Rehabilitation;CMT= Charcot-Marie-Tooth;DSP= distal symmetric polyneuropathy;EDX= electrodiagnostic;GTT= glucose tolerance testing;IFE= immunofixation electrophoresis;QSS= Quality Standards Subcommittee;SPEP= serum protein electrophoresis.

Background: Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of autonomic testing, nerve biopsy, and skin biopsy for the assessment of polyneuropathy. Methods: A literature review using MEDLINE, EMBASE, and Current Contents was performed to identify the best evidence regarding the evaluation of polyneuropathy published between 1980 and March 2007. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based upon the level of evidence. Results and Recommendations: 1) Autonomic testing should be considered in the evaluation of patients with polyneuropathy to document autonomic nervous system dysfunction (Level B). Such testing should be considered especially for the evaluation of suspected autonomic neuropathy (Level B) and distal small fiber sensory polyneuropathy (SFSN) (Level C). A battery of validated tests is recommended to achieve the highest diagnostic accuracy (Level B). 2) Nerve biopsy is generally accepted as useful in the evaluation of certain neuropathies as in patients with suspected amyloid neuropathy, mononeuropathy multiplex due to vasculitis, or with atypical forms of chronic inflammatory demyelinating polyneuropathy (CIDP). However, the literature is insufficient to provide a recommendation regarding when a nerve biopsy may be useful in the evaluation of DSP (Level U). 3) Skin biopsy is a validated technique for determining intraepidermal nerve fiber density and may be considered for the diagnosis of DSP, particularly SFSN (Level C). There is a need for additional prospective studies to define more exact guidelines for the evaluation of polyneuropathy. Neurology ® 2009;72:177–184

Introduction: Paroxysmal sympathetic storm (PSS) is a rare syndrome characterized by episodic hypertension, hyperhydrosis, hyperthermia, tachycardia, tachypnea, and extensor posturing. Case reports: This article describes two cases of PSS: one following traumatic brain injury and the other following cardiac arrest. Discussion: The first responded to labetalol, morphine, and codeine, whereas the second responded to labetalol. Conclusion: These observations underscore the importance of central opioid receptors and nonselective β-adrenergic antagonists in modulating catecholamine pathways

The objective of this report was to develop a case definition of distal symmetric polyneuropathy to standardize and facilitate clinical research and epidemiologic studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetric polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiologic studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach to defining distal symmetric polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiologic research studies will ensure greater consistency of case selection.

England JD, Gronseth GS, Franklin G, Miller RG, Asbury AK, Carter GT, Cohen JA, Fisher MA, Howard JF, Kinsella LJ, Latov N, Lewis RA, Low PA, Sumner AJ. Distal symmetrical polyneuropathy: a definition for clinical research. A report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. The objective of this report was to develop a case definition of "distal symmetrical polyneuropathy" to standardize and facilitate clinical research and epidemiologic studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetrical polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiologic studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach to defining distal symmetrical polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiologic research studies will ensure greater consistency of case selection.

A man with a subclinical cobalamin deficiency developed syncope, vertigo, paresthesias, and ataxia after two exposures to nitrous oxide anesthesia. Patients with unrecognized cobalamin deficiency may be particularly susceptible to brief exposures to nitrous oxide, which inactivates the cobalamin-dependent enzyme methionine synthase and may cause a myeloneuropathy. Clinicians should consider this entity when confronted with patients with neuropathic symptoms after surgical or dental procedures.

We report a case of severe orthostatic hypotension in a 60-year-old patient with Down's syndrome presumably due to spinal cord compression secondary to atlantoaxial instability that resolved following surgical decompression; the mechanism of disease may be selective damage to the autonomic descending fibers.

Reply from the Authors: We acknowledge the omission of urinary methylmalonate (MMA) as a test for diagnosis of cobalamin (Cbl) deficiency in our recent editorial on the diagnosis of cobalamin deficiency [1] and we thank Dr. Norman and Dr. Cronin for pointing this out. We certainly concede that urine MMA provides information that is of similar clinical value to that derived from measurement of serum MMA but we do not agree with the contention that urinary MMA is the most accurate test, nor that it should be the initial screening test, for identifying Cbl deficiency. We believe that serum MMA assay does offer several practical advantages over the urine assay. [2] The first is the …

Neurogenic causes of pruritus and a rash are uncommon. We report a patient with dermatomal pruritus and a rash who had a cervicothoracic syrinx and a thoracic spinal cord tumor. We believe the syrinx interrupted fibers subserving itch, resulting in dermatomal pruritus with secondary scratching and a rash.