Mathew Alexander

Clinical and laboratory features and response to treatment in patients presenting with vitamin B12 deficiency-related neurological syndromes.

AIMS AND OBJECTIVES To study the clinical and laboratory features of patients admitted with vitamin B12 deficiency-related (B12def) neurological syndromes. SETTINGS AND DESIGN A hospital-based retrospective and prospective study conducted at a referral teaching hospital. MATERIALS AND METHODS Consecutive patients admitted with vitamin B12 deficiency-related neurological disorders during a three-year period from June 2000 to May 2003 were included. Data regarding clinical and laboratory features were obtained. Follow-up was done at least six months following treatment with parenteral vitamin B12. Chi-square test was used for statistical analysis. RESULTS A total of 63 patients (52 males) with a mean age of 46.2 years were studied. The mean duration of symptoms at presentation was 10.3 months. Myeloneuropathy (54%) was the commonest neurological manifestation, followed by myeloneuropathy with cognitive dysfunction (34%), and peripheral neuropathy (9%). Neuropsychiatric manifestations and dementia were observed in 38% and 19% of patients respectively. All the patients had megaloblastic changes in the bone marrow smear. Eleven (17.5%) patients had both hemoglobin and the mean corpuscular volume (MCV) within the normal range. Follow-up after at least six months of therapy with parenteral B12 showed improvement in 54% patients. CONCLUSIONS A high index of suspicion of B12def is required in patients presenting with myelopathy, cognitive decline, or neuropathy. A normal hemoglobin or MCV does not exclude B12def; therefore, other tests such as bone marrow smear and serum vitamin B12 assay are essential, as the condition is often reversible with treatment.

Postinfectious pandysautonomia with complete recovery after intravenous immunoglobulin therapy

Acute dysfunction of the autonomic nervous system was first reported as severe parasympathetic and sympathetic failure without other neurologic manifestations by Young et al.1 in 1969. Since then, several other cases have been described.2-6 The characteristic features of this syndrome include severe orthostatic hypotension, impaired gastrointestinal and bladder motility, dry mucous membranes, and loss of sweating ability with impaired pupillary light reflex and accommodation reflex. These features are similar to those seen in Guillain-Barre syndrome (GBS) accompanied by autonomic disturbances. However, in pandysautonomia, there is no clinical or neurophysiological evidence for involvement of the somatic nerve fibers. Acute pandysautonomia is increasingly recognized as a possible variant of GBS. The presence of raised CSF protein and varying degrees of sensory loss and dysesthesias2,3 lends credence to this belief. IV immunoglobulin (Ig) is of benefit in GBS,7 and it seems reasonable to expect that pandysautonomia should also show a favorable response. …

Decompressive craniectomy in cerebral venous thrombosis: a single centre experience

Background Cerebral venous thrombosis (CVT) is an important cause for stroke in the young where the role for decompressive craniectomy is not well established. Objective To analyse the outcome of CVT patients treated with decompressive craniectomy. Methods Clinical and imaging features, preoperative findings and long-term outcome of patients with CVT who underwent decompressive craniectomy were analysed. Results Over 10 years (2002–2011), 44/587 (7.4%) patients with CVT underwent decompressive craniectomy. Diagnosis of CVT was based on magnetic resonance venography (MRV)/inferior vena cava (IVC). Decision for surgery was taken at admission in 19/44 (43%), within 12 h in 5/44 (11%), within first 48 h in 15/44 (34%) and beyond 48 h in 10/44 (22%). Presence of midline shift of ≥10 mm (p<0.0009) and large infarct volume (mean 146.63 ml; SD 52.459, p<0.001) on the baseline scan influenced the decision for immediate surgery. Hemicraniectomy was done in 38/44 (86%) and bifrontal craniectomy in 6/44 (13.6%). Mortality was 9/44 (20%). On multivariate analysis (5% level of significance) age <40 years and surgery within 12 h significantly increased survival. Mean follow-up was 25.5 months (range 3–66 months), 26/35 (74%) had 1 year follow-up. Modified Rankin Scale (mRs) continued to improve even after 6 months with 27/35 (77%) of survivors achieving mRs of ≤2. Conclusions This is the largest series on decompressive craniectomy for CVT in literature to date. Decompressive craniotomy should be considered as a treatment option in large venous infarcts. Very good outcomes can be expected especially if done early and in those below 40 years.

Acute disseminated encephalomyelitis: Treatment guidelines

Acute disseminated encephalomyelitis (ADEM) is a monophasic, postinfectious or postvaccineal acute inflammatory demyelinating disorder of central nervous system (CNS).[1,2] The pathophysiology involves transient autoimmune response directed at myelin or other self-antigens, possibly by molecular mimicry or by nonspecific activation of autoreactive T-cell clones.[3] Histologically, ADEM is characterized by perivenous demyelination and infiltration of vessel wall and perivascular spaces by lymphocytes, plasma cells, and monocytes.[4] The annual incidence of ADEM is reported to be 0.4–0.8 per 100,000 and the disease more commonly affects children and young adults, probably related to the high frequency of exanthematous and other infections and vaccination in this age group.[5–9] There seems to be no gender predominance.[10]

Cranial nerve involvement in patients with leprous neuropathy.

BACKGROUND Leprosy is one of the most common causes of peripheral neuropathy, perhaps closely matched by diabetic neuropathy. Patterns of peripheral neuropathy in leprosy can be varied, which may include mononeuropathy, mononeuritis multiplex and symmetric polyneuropathy. Cranial nerves, especially facial and trigeminal nerves, are also commonly involved in leprosy. AIMS To find out the pattern and spectrum of cranial nerve involvement in a consecutive series of patients with leprous neuropathy. SETTINGS AND DESIGN A retrospective review of patients admitted with leprosy to the Neurology Department of a tertiary care center. MATERIALS AND METHODS All consecutive patients admitted during an 8-year period (1995-2003) and diagnosed to have leprosy were included. They were clinically evaluated to determine the frequency and pattern of cranial nerve involvement. RESULTS About 18% (9/51) of the leprosy patients seen during that period had clinical evidence of cranial nerve involvement. Facial and trigeminal nerves were the most commonly affected (five and four patients respectively). CONCLUSIONS Cranial nerve involvement is common in leprosy, which emphasizes the need to carefully examine them. Also, one should exclude leprosy in patients presenting with isolated cranial neuropathies.

Underlying prothrombotic states in pregnancy associated cerebral venous thrombosis

BACKGROUND The exact pathogenesis of pregnancy associated cerebral venous thrombois is still unsettled. Aims : To identify possible inherited and acquired prothrombotic risk factors and also identify the factors associated with mortality in pregnancy associated CVT. SETTINGS AND DESIGN Prospective cohort study to identify prothrombotic risk factors and case control study of influence of local traditional practice of puerperal water restriction on postpartum CVT. MATERIALS AND METHODS Consecutive patients with pregnancy associated CVT seen over a period of three years. Thrombotic workup included genetic markers, protein assays, and other factors. STATISTICAL ANALYSIS Univariate and chi-square analysis. RESULTS Of the 41 patients studied during the study period, 71% of patient had a single and 34% had multiple prothrombotic risk factors. Methylene tetrahydro-folate reductase (MTHFR) heterozygosity (19.5%) and factor V Leiden heterozygous (7.3%) were the commonest genetic markers. Hyperhomocysteinemia (34%) and elevated factor VIII levels (14.6%) were the other important risk factors. In this cohort the mortality was 17%. Mortality increased by odds of 1.3 for every additional prothrombotic marker. The factors associated with increased mortality included: status epileptics (P = 0.05, OR 13.2, 95% CI 1.002 - 173), deep venous system involvement (P = 0.016, OR 9.64, 95% CI 1.53 - 60.6), presence of midline shift (P = 0.012, OR 24.7, 95% CI 2.05 - 29.8) and diffuse cerebral edema (P = 0.006, OR 14.5, 95% CI 2.18- 96.4). The traditional practice of decrease intake of water during puerperium was significant in woman with pregnancy associated CVT when compared to control subjects (P < 0.02). CONCLUSION In patients with pregnancy associated CVT, prothrombotic markers can be multiple and are associated with increased odds of mortality. Deep venous system involvement, presence of midline shift and diffuse cerebral edema increased mortality. Peuperial water restriction may be a modifiable risk factor.

Oxidative Stress, NF-κB and the Ubiquitin Proteasomal Pathway in the Pathology of Calpainopathy

The neuromuscular disorder, calpainopathy (LGMD 2A), is a major muscular dystrophy classified under limb girdle muscular dystrophies. Genetic mutations of the enzyme calpain 3 cause LGMD 2A. Calpainopathy is phenotypically observed as progressive muscle wasting and weakness. Pathomechanisms of muscle wasting of calpainopathy remain poorly understood. Oxidative stress, NF-κB and the ubiquitin proteasomal pathway underlie the pathology of several muscle wasting conditions but their role in calpainopathic dystrophy is not known. Oxidative and nitrosative stress, the source of reactive oxygen species, NF-κB signaling and protein ubiquitinylation were studied in 15 calpainopathic and 8 healthy control human muscle biopsies. Oxidative stress and NF-κB/IKK β signaling were increased in calpainopathic muscle and may contribute to increased protein ubiquitinylation and muscle protein loss. Preventing oxidative stress or inhibition of NF-κB signaling could be considered for treatment of LGMD 2A.

Pulmonary Distress Following Attempted Suicidal Hanging

OBJECTIVE To assess the incidence of post-hanging pulmonary distress in cases of attempted suicidal hanging and predictors of outcome among these patients. DESIGN Five-year retrospective analysis. SETTING Tertiary care center in south India. PATIENTS A total of 335 patients who attempted suicidal hanging, aged above 16 years, were admitted during this period. Thirty-eight of them with pulmonary distress established clinically and with radiological evidence of pulmonary injury post hanging met the inclusion criteria. MEASUREMENTS Data from ICU records of 5 years, X-rays and laboratory investigations were reviewed. In patients identified to have post-hanging pulmonary distress, the neurological status, chest x-rays, arterial blood gas values and outcome data were collected and analyzed. RESULTS Eleven percent (n = 38) of the 335 patients admitted following attempted suicidal hanging were diagnosed to have post-hanging pulmonary distress. The overall mortality among post-hanging patients was 5%, which increased to 34.2% (n = 13) in the presence of pulmonary distress (P < or = 0.001). Among the prognostic factors evaluated, a PaO 2 / FiO 2 (P/F) ratio of < 100 at admission predicted a poor outcome (P < or = 0.001). CONCLUSION Post-hanging pulmonary distress is a relatively common complication of hanging and is associated with increased mortality. P/F ratio from arterial blood gas at admission was the only significant predictor of outcome in this group of patients.

Involvement of oxidative stress, nuclear factor kappa B and the ubiquitin proteasomal pathway in dysferlinopathy.

AIMS Dysferlinopathies are autosomal recessive neuromuscular disorders arising from mutations of the protein dysferlin that preferentially affect the limbs which waste and weaken. The pathomechanisms of the diseases are not known and effective treatment is not available. Although free radicals and upstream signaling by the redox sensitive transcription factor, NF-κB, in activation of the ubiquitin pathway are shown to occur in several muscle wasting disorders, their involvement in dysferlinopathy is not known. This study analyzed the role of oxidative stress, NF-κB and the ubiquitin pathway in dysferlinopathic muscle and in dysferlin knockdown human myoblasts and myotubes. MAIN METHODS Fourteen dysferlinopathic muscle biopsies and 8 healthy control muscle biopsies were analyzed for oxidative stress, NF-κB activation and protein ubiquitinylation and human primary myoblasts and myotubes knocked down for dysferlin were studied for their state of oxidative stress. KEY FINDINGS Dysferlinopathic muscle biopsies showed NF-κB p65 signaling induced protein ubiquitinylation in response to oxidative stress. Dysferlin knock down primary muscle cell cultures confirmed that oxidative stress is induced in the absence of dysferlin in muscle. SIGNIFICANCE Anti-oxidants that also inhibit nitrosative stress and NF-κB activation, might prove to be of therapeutic benefit in slowing the progression of muscle wasting that occurs with dysferlinopathy.

Mechanical thrombectomy for acute ischemic stroke in pregnancy using the penumbra system

Even though intravenous thrombolysis with tissue plasminogen activator (IV tPA) is the standard of care in acute ischemic stroke, its use in pregnancy is not clearly defined. Mechanical thrombectomy devices can be an option; however, literature on the use of such mechanical devices in stroke in pregnancy is lacking. Here we describe two cases that developed acute embolic stroke during pregnancy who were successfully treated by mechanical clot retrieval using the Penumbra system 28 (Penumbra Inc., Alameda, California, USA). To the best of our knowledge, these are the only case reports on the use of the Penumbra device in pregnant patients with acute ischemic stroke.