Isoniazid exposure and pyridoxine levels in human immunodeficiency virus associated distal sensory neuropathy.

SETTING: Distal sensory polyneuropathy (DSP) may manifest in human immunodeficiency virus (HIV) infected individuals before or after antiretroviral therapy (ART). DSP can also occur in response to isoniazid (INH); this can be prevented by pyridoxine supplementation. N-acetyltransferase 2 (NAT2) polymorphisms influence drug acetylation and possibly the risk for INH-associated DSP. OBJECTIVE: To investigate the relationship between previous/current TB, pyridoxine deficiency and DSP in HIV-infected individuals enrolled in a government-sponsored HIV programme. DESIGN: Neuropathy assessments were performed among 159 adults pre-ART and 12 and 24 weeks thereafter. DSP was defined as ⩾1 neuropathic symptom and sign. NAT2 genotypes predicted acetylation phenotype. Serum pyridoxine levels (PLP) were quantified at baseline and week 12. RESULTS: DSP was present in 16% of individuals pre-ART and was associated with previous/current TB (P = 0.020). Over 50% were pyridoxine deficient (PLP < 25 nmol/l), despite supplementation with vitamin B complex supplements (2-4 mg/day pyridoxine). Those with a history of TB and pre-ART DSP were more likely to be pyridoxine deficient (P = 0.029), and slow/intermediate NAT2 phenotypes impacted on their PLP levels. Incident/worsening DSP after ART developed in 21% of the participants. PLP levels remained low after ART, particularly among those with prior TB, but without an association between DSP or NAT2 phenotypes. CONCLUSION: Adequate pyridoxine supplementation before ART initiation should be prioritised, particularly in those with a history of TB or current TB.

Radial artery pseudoaneurysm: a rare complication after arthroscopic treatment of a volar wrist ganglion in a hemophilia patient.

Vascular complications of wrist arthroscopy are rare. We report the case of a 42-year-old male patient with a history of hemophilia who had a ganglion located where the radial pulse is taken that had been causing him pain for five months. After infusion of Exacyl (antifibrinolytic agent), the ganglion was drained arthroscopically. Fifteen days later, the patient presented with a pseudoaneurysm of the radial artery requiring urgent reoperation.

Sensory polyneuropathy in human immunodeficiency virus-infected patients receiving tuberculosis treatment.

SETTING: Human immunodeficiency virus (HIV) infection and treatments for HIV infection and tuberculosis (TB) are associated with the risk of developing sensory polyneuropathy (SPN). Vitamin B6 and genetically determined slow isoniazid (INH) acetylation are believed to play key roles in the development of SPN in a TB treatment setting. OBJECTIVE: To investigate slow acetylation and risk factors for SPN in HIV-infected patients receiving TB treatment, and establish vitamin B6 status and its association with SPN. METHODS: HIV-infected in-patients were prospectively assessed after initiating TB treatment and vitamin B6 supplementation, and monthly during hospitalisation. SPN was defined as ≥1 symptom plus ≥1 sign. NAT2 genotyping predicted acetylation status, and plasma high performance liquid chromatography estimated vitamin B6 status. A survival analysis estimated hazard ratios (HRs) for SPN during TB treatment. RESULTS: Of 116 participants, 56% had SPN at study entry. Participants developed SPN at a rate of 26/100 person-months (95%CI 18-35) during TB treatment, which was independently associated with slow acetylation (HR 2.5; 95%CI 1.1-5.9), as well as black race, previous TB and extra-pulmonary/disseminated TB. Vitamin B6 status was normal, irrespective of SPN. CONCLUSIONS: Risk factors for SPN suggest a multi-factorial pathogenesis related to INH and other potential nervous system insults. SPN developed despite normal vitamin B6 status, suggesting other mechanisms of injury.

Impact of preoperative radiotherapy on head and neck free flap reconstruction: a report on 429 cases.

BACKGROUND: The primary objective of this study was to evaluate the impact of preoperative radiotherapy on the outcomes of head and neck microvascular reconstruction. The secondary objective was to assess the specific effects of irradiation doses (IDs) ≥60 Gy on the outcomes of head and neck microvascular reconstruction. METHODS: All patients who underwent head and neck free-flap reconstruction in our institution between 2000 and 2010 were included in this retrospective study. A total of 429 patients were enrolled including 136 patients previously irradiated on the head and neck. The impact of preoperative radiotherapy on free-flap success, local and general complications, postoperative mortality, time of decannulation, duration of enteral nutrition and length of stay was assessed in univariate and multivariate analyses. RESULTS: In multivariate analysis, preoperative radiotherapy (irrespective of ID) was a significant risk factor for fistula formation (p = 0.003) and wound infection (p = 0.005). Previous neck irradiation at doses ≥60 Gy was associated with an increased risk of free-flap failure (p = 0.04), overall local complications (p = 0.05), haematoma (p = 0.04) and longer duration of enteral nutrition (p = 0.006) and hospital stay (p = 0.004). CONCLUSIONS: Preoperative radiotherapy, particularly for ID ≥ 60 Gy, is one of the main determinants of the outcomes of head and neck microvascular reconstruction.

[Interest and reliability of frozen section biopsy in the treatment of skin tumors]. / Intérêt et fiabilité de l'examen extemporané dans la prise en charge des tumeurs cutanées.

INTRODUCTION: Association of surgical treatment combined to frozen section biopsies appears to be one of the most appropriate therapeutic solution for the treatment of skin carcinomas. We report our experience on 269 tumors assessed with frozen sections. Our goal was to first study the benefit of a one-time surgical approach, then to better target the tumors eligible for this examination and finally to number the difference between frozen section and final histology studies. MATERIALS AND METHODS: This is a retrospective analysis of 269 tumors, operated on an outpatient basis with frozen section followed later by a final histology study. All being performed by the same team of surgeons and pathologist. Only previously biopsied and diagnosed basal cell or squamous cell tumors were included. The recorded data were: location of tumor; histological type; involved margins; number of cuts; differences between frozen section and final histological studies, which conduct to a two-time surgical approach; number of tumors for which frozen section was impossible during surgery and that lead to a two-time surgical approach; type of reconstruction; number of recurrence. RESULTS: The follow up was 48 months (26.6 to 78.1). Histogical analyses were carried on basal cell carcinoma (92%), squamous cell carcinoma (8%) with a topographic distribution mainly in face and neck (72%). Of the 269 tumors excised, 207 representing 77% had a sufficient safety margin, 62 representing 23% had at least one invaded bank that required further surgical resection. We found seven cases of two-time surgical approach. In three cases, it was secondary to medical decision because of a technical difficulty of histologists. In one case, histological diagnosis can't be obtained by frozen section study. In three cases, we found a difference between frozen section and final study. CONCLUSION: The benefit provided by the frozen section takes its value in the treatment of face and neck tumors, whose optimal margins are sometimes difficult to obtain and minimal scar ransom necessary. A one-time surgery was made possible to us thanks to this fast examination. The low rate of second surgery and recurrence allows us to demonstrate the reliability of this technique.

[Study of skin retraction applied to the treatment of skin tumors. Mapping of the human body]. / Étude de la rétraction cutanée appliquée à la prise en charge des tumeurs cutanées. Cartographie du corps humain.

SUBJECT: Skin, the main organ of the human body, is equipped with own biomechanical characteristics, highly variable depending on intra-individual factors (location, weight status, dermatological diseases…) and interindividual (age, sex…). Despite some recent cutometric studies, our review of the literature shows that there is no currently reliable analytical model representing the biomechanical behavior of the skin. Yet, this is a central issue in dermatology surgery, especially in the treatment of skin tumors, for the proper observance of surgical margins. PATIENTS AND METHODS: We studied prospectively on 75 resection specimens (about 71 patient(s)), for the treatment of skin lesions tumor suspicious or known malignant or benign. Room dimensions were measured before and 5 minutes after excision, leading us to calculate a ratio of retraction of the skin surface. This retraction was correlated with age, gender, tumor type, and anatomic location of the site of excision. RESULTS: The power of retraction of the skin varies significantly by region of the body. It is maximum in the upper limb (hand excluded) and in the cervical region. At the cephalic region, skin of the ear and periorbital skin have capacities of important early retraction. Unlike the lower limb (foot excluded), the back skin of the nose and face appear to be a minimum of shrinkage. Age also seems to change on that capacity shrinkage, sex would have no influence. CONCLUSION: Our study confirms the variations in the ability of skin retraction based on a number of factors. In dermato-oncology, that power retraction could cause significant differences between clinical surgical margins and final pathologist margins. We believe it must be taken into account by the couple surgeon-pathologist, especially in the context of invasive and/or recurrent tumors.

Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at risk for familial ALS.

OBJECTIVE: It has been speculated that amyotrophic lateral sclerosis (ALS) is characterized by a premanifest period during which neurodegeneration precedes the appearance of clinical manifestations. Magnetic resonance spectroscopy (MRS) was used to measure ratios of neurometabolites in the cervical spine of asymptomatic individuals with a mutation in the SOD1 gene (SOD1+) and compare their neurometabolic ratios to patients with ALS and healthy controls. METHODS: A cross-sectional study of (1)H-MRS of the cervical spine was performed on 24 presymptomatic SOD1+ volunteers, 29 healthy controls, and 23 patients with ALS. All presymptomatic subjects had no symptoms of disease, normal forced vital capacity, and normal electromyographic examination. Relative concentrations of choline (Cho), creatine (Cr), myo-inositol (Myo), and N-acetylaspartate (NAA) were determined. RESULTS: NAA/Cr and NAA/Myo ratios are reduced in both SOD1+ subjects (39.7%, p = 0.001 and 18.0%, p = 0.02) and patients with ALS (41.2%, p < 0.001 and 24.0%, p = 0.01) compared to controls. Myo/Cr is reduced (10.3%, p = 0.02) in SOD1+ subjects compared to controls, but no difference was found between patients with ALS and controls. By contrast, NAA/Cho is reduced in patients with ALS (24.0%, p = 0.002), but not in presymptomatic SOD1+ subjects compared to controls. CONCLUSIONS: Changes in neurometabolite ratios in the cervical spinal cord are evident in presymptomatic SOD1+ individuals in advance of symptoms and clinical or electromyographic signs of disease. These changes reflect a reduction in NAA/Cr and NAA/Myo. Neurometabolic changes in this population resemble changes observed in patients with clinically apparent ALS. This suggests that neurometabolic changes occur early in the course of the disease process.

Multipoint incremental motor unit number estimation as an outcome measure in ALS.

BACKGROUND: Improved outcome measures are necessary to reduce sample size and increase power in amyotrophic lateral sclerosis (ALS) clinical trials. Motor unit number estimation (MUNE) is a potentially attractive tool. MUNE methods previously employed in multicenter trials exhibited excessive variability and were prone to artifact. OBJECTIVE: To evaluate a modification of standard incremental MUNE in a multicenter natural history study of subjects with ALS. METHODS: Fifty healthy subjects were evaluated twice and 71 subjects with ALS were studied repeatedly for up to 500 days. Side and nerve studied was based on clinical examination findings. Nerves were stimulated at 3 specified locations and 3 increments were obtained at each location. Average single motor unit action potential (SMUP) amplitude was calculated by adding the amplitude of the third increment at each location and dividing by 9; SMUP was divided into maximum CMAP amplitude to determine the MUNE. RESULTS: Test-retest variability was 9% in normal subjects. Average MUNE for normal subjects was 225 (±87), and was 41.9 (±39) among subjects with ALS at baseline. Subjects with ALS showed clear decrements over time, with an overage rate of decline of approximately 9% per month. SMUP amplitude increased with time in a fashion consistent with the known pathophysiology of ALS. CONCLUSION: Multipoint incremental MUNE has a number of attributes that make it attractive as an outcome measure in ALS and other diseases characterized by motor unit loss. It can be rapidly performed on any EMG machine and has repeatability and rates of decline that favorably compare to other previously described methods.

Polyneuropathy, anti-tuberculosis treatment and the role of pyridoxine in the HIV/AIDS era: a systematic review.

Tuberculosis (TB) is increasing in incidence in certain parts of the world, particularly where there is a co-epidemic of human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS), and it is associated with a significant degree of morbidity and mortality. One of the most common complications of anti-tuberculosis treatment is the development of a painful isoniazid (INH) associated polyneuropathy (PN), which is preventable with adequate pyridoxine supplementation. As PN is also the most frequent neurological complication associated with HIV infection, subjects who are HIV and TB co-infected may be at increased risk of developing PN. In this review, we explore current knowledge of anti-tuberculosis drug associated PN focusing on INH and its relationship to pyridoxine, as well as the additional impact of antiretroviral treatment and TB-HIV co-infection. It is evident that guidelines established for the prevention and treatment of this problem differ between industrialised and developing countries, and that further research is needed to define the optimum dosing of pyridoxine supplementation in populations where there is a significant burden of TB and HIV.

Clinical, electrophysiologic, and pathologic evidence for sensory abnormalities in ALS.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of upper and lower motor neurons. Reports of the nature and frequency of sensory nerve involvement in ALS have varied. METHODS: We reviewed the Emory University motor neuron disease registry between 1997 and 2004 to identify 103 patients with ALS without coexisting diseases that might cause sensory abnormalities and for whom electrodiagnostic studies were available for review. Neurophysiologic studies were interpreted based on age-adjusted normative data from our laboratory. Twelve control biopsies were evaluated alongside 22 samples from patients with ALS to ensure blinded evaluation of pathologic specimens. RESULTS: Sensory symptoms or signs were present in 32% of patients, sural sensory nerve action potential amplitudes were abnormal in 27%, and pathologic abnormalities were present in 91% of patients. Large-caliber myelinated fibers were predominantly affected (reduced in 73%) and small-caliber myelinated fibers were affected less often (23%). Thinly myelinated fibers were present in 95% and regenerating clusters in 77% of the biopsies. Teased fiber analysis showed an increased frequency of axonal degeneration and regeneration as well as excessive myelin irregularity. Morphometry confirmed the loss of large-caliber fibers. CONCLUSIONS: These data indicate that one third of patients with amyotrophic lateral sclerosis report sensory symptoms and sural sensory response amplitudes are reduced in a similar proportion of subjects. Pathologic evidence of sensory nerve pathology was present in 91% of patients who underwent sural nerve biopsy. The electrophysiologic and pathologic findings indicate a pattern of axonal loss that predominantly affects large-caliber myelinated fibers.

Medical and surgical treatment for ocular myasthenia.

BACKGROUND: Approximately 50% of people with myasthenia gravis present initially with purely ocular symptoms, so called ocular myasthenia and between 50 to 60% of these people will progress to develop generalized disease. The vast majority will do so within the first one to two years. There is controversy surrounding the appropriate management of patients with ocular myasthenia. OBJECTIVES: To perform a systematic review of the literature relevant to the treatment of ocular myasthenia and to answer three specific questions. Are there any medical or surgical treatments that have an impact on the risk of progression from ocular to generalized myasthenia gravis? Are there any medical or surgical treatments that improve symptoms of diplopia or ptosis in ocular myasthenia? What is the frequency of side effects associated with treatments used in people with ocular myasthenia? SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (searched December 2004), MEDLINE (1996 to 2004) and EMBASE (1980 to 2004) for randomized controlled trials as well as case-control and cohort studies. The titles and abstracts of all articles were read by both authors and the full text of all articles that were of possible relevance was reviewed in full. The references of all manuscripts included in the review were scanned to identify additional articles of relevance and experts in the field were contacted to identify additional published and unpublished data. Where necessary and possible, we contacted authors for further information. SELECTION CRITERIA: To be included in the review, studies had to meet three criteria: (a) randomized (or quasi-randomized) controlled study design; (b) active treatment compared to placebo, no treatment or some other treatment; and (c) results reported separately for patients with ocular myasthenia (grade 1) as defined by the Myasthenia Gravis Foundation of America. DATA COLLECTION AND ANALYSIS: We collected data regarding the risk of progression to generalized myasthenia gravis, improvement in ocular symptoms, and the frequency of treatment-related side effects. MAIN RESULTS: We identified two randomized controlled trials relevant to the treatment of ocular myasthenia, only one of which reported results in terms of the pre-specified outcome measures used in this review. This study included only three participants and was of limited methodological quality. In the absence of data from randomized controlled trials, we present a review of the available observational data. AUTHORS' CONCLUSIONS: There are no data from randomized controlled trials on the impact of any form of treatment on the risk of progression from ocular to generalized myasthenia gravis. The available randomized controlled literature does not permit any meaningful conclusions about the efficacy of any form of treatment for ocular myasthenia. Data from several reasonably good quality observational studies suggest that corticosteroids and azathioprine may be beneficial in reducing the risk of progression to generalized myasthenia gravis.

A pain in the fetus: toward ending confusion about fetal pain.

Are fetuses, at any stage of their development, capable of feeling pain? In his paper, "Locating the Beginnings of Pain," Stuart Derbyshire argues that they are not. We argue that he reaches this conclusion by way of conceptual confusion, a misreading of the available scientific data and the inclusion of irrelevant data. Despite his assertion to the contrary, the work of most scientists in the area supports the conclusion that fetuses can feel pain. At the outset we examine the concept of pain and distinguish it from the allied concept of nociception, with which it is sometimes confused. With the relevant conceptual framework in place, we elucidate the problem of determining when, in its development, a human becomes capable of feeling pain. We then examine the available data showing how, on balance, it tends more to support than undermine the claim that fetuses of around 28 to 30 weeks' gestation are capable of feeling pain.

Presynaptic neuronal antigens expressed by a small cell lung carcinoma cell line.

Small cell lung carcinoma (SCLC) is a tumour of neuroendocrine origin often found in association with autoimmune paraneoplastic neurological disorders. We established a SCLC cell line from a woman with Lambert-Eaton myasthenic syndrome (LEMS) who developed antibodies to both the P/Q-type voltage-gated calcium channels (VGCC) and the muscle acetycholine receptor (AChR). We used a range of techniques to establish which neuronal antigens were expressed in her tumour cell line. The results show that many proteins involved in exocytosis are present in the SCLC cells, and that depolarisation-dependent release of [(3)H]-serotonin is linked to calcium influx through P/Q-type VGCCs. In addition, some of the subunits encoding the AChR and both agrin and ARIA, molecules released from the motor nerve during development, were expressed. These results suggest that many potential antigenic targets are present in SCLC, and indicate a surprising 'motor nerve terminal'-like characteristic of this line.

Neurological potassium channelopathies.

Potassium channel dysfunction has been implicated in a variety of genetic and acquired neurological disorders that are collectively referred to as the potassium channelopathies. These include acquired neuromyotonia, episodic ataxia type-1, hereditary deafness syndromes, benign familial neonatal convulsions and hypokalaemic periodic paralysis. Insight into potassium channel structure and function is crucial to understanding the pathophysiology of these conditions. This article describes potassium channel structure and function and then outlines what is known about the immunology and genetics of the neurological potassium channelopathies.

Antiepileptic drug-induced visual hallucinations in a child.

The neurologic signs and symptoms of carbamazepine and phenytoin toxicity, such as ataxia, dysarthria, and nystagmus, are well known. The psychiatric manifestations of toxicity, such as psychosis and hallucinations, however, are less widely recognized. This study reports the case of a 9-year-old male with seizures who developed intermittent complex visual hallucinations after therapy with antiepileptic drugs was begun. This study considered seizures, migraine, underlying psychiatric diathesis, and drug toxicity as possible etiologies but after extensive investigation concluded that his symptoms were most likely a drug side effect.

Human immunodeficiency virus-associated pure motor lumbosacral polyradiculopathy.

BACKGROUND: Neuromuscular disease is a common manifestation of human immunodeficiency virus infection and acquired immunodeficiency syndrome, but isolated and severe pathology confined to the motor roots or anterior horn cells are not a recognized clinical entity. OBJECTIVE: To describe the novel clinical presentation of human immunodeficiency virus-related polyradiculopathy manifesting as isolated severe motor symptoms confined to the legs. DESIGN: A case series comprising 4 patients identified prospectively during a 6-month period. SETTING: Patients were seen in the Department of Neurology, Groote Schuur Hospital, Cape Town, South Africa. This is an 800-bed teaching hospital, with approximately 5000 patients seen annually in the Department of Neurology. PATIENTS: Patients were identified by their unique presentation with a severe isolated motor neuropathy in the lower limbs. All were Xhosa-speaking African women. RESULT: Early human immunodeficiency virus infection may be associated with pure motor lumbosacral polyradiculopathy. CONCLUSION: It remains unclear whether this clinical syndrome should be regarded as a variant of the Guillain-Barre syndrome or whether it represents a unique disorder associated with early human immunodeficiency virus infection.