Extensor Plantar Reflex Research Articles

SPG15: a cause of juvenile atypical levodopa responsive parkinsonism

Autosomal recessive hereditary spastic paraplegias with thin corpus callosum (AR HSP-TCC) are rare and complex neurodegenerative disorders characterized by a genetic heterogeneity of which several genes (SPG11 and SPG15, SPG21, SPG47) or loci (SPG32, SPG46) have been identified. In SPG15, additional features have been described [1]: mental retardation, motor neuropathy, dysarthria and pigmentary maculopathy and recently, in a single family with a new homozygous mutation, parkinsonism [2]. In order to further confirm that SPG15 should be considered in the diagnosis of juvenile atypical parkinsonism, we describe another patient affected with SPG15, including juvenileonset levodopa-responsive parkinsonism. A female of Portuguese origin with consanguinity was 17 years old when referred to our center following 12 months of gait difficulties. The patient’s history included mild dysarthria and scholarly delay. Clinical examination demonstrated spastic paraplegia with bilateral extensor plantar reflexes and mild proximal motor deficit in the lower limbs. Vertical saccades were slightly hypometric. By age 19, a left upper limb rest tremor had developed as well as moderate bilateral akinesia, hypertonia, and hypomimia (video). An acute levodopa challenge (250 mg) led to a 60 % improvement of United Parkinson disease rating scale motor score (UPDRSIII) devoted to upper limbs (items 20–25, from 8/24 to 3/24). Rest tremor disappearance was sustained with a levodopa daily dose of M. Anheim and C. Tranchant contributed equally to the work and should be considered as co-last authors.

Neurological involvement in Primary Sjogren Syndrome: A case report

Introduction: Primary Sjogren Syndrome (PSS) is an autoimmune mediated inflammatory disease, which may affect, aside from exocrine glands, other organs/systems, including the nervous system (both peripheral and central). CASE: The authors hereby report a case of a 67year old woman, admitted due to hypoesthesia of the left foot, which progressively ascended to the infra-mammary region within a period of 7days, weakness of both legs, constipation and xerophtalmia. Neurological examination showed diminished strength, grade 3 of both legs; ataxia; extensor plantar reflexes;and hypoesthesia from D5–D9.

Autoimmune diseases go well together — Multiple autoimmune syndrome type 3

CO RR EC TE D PR OO F ataxia; extensor plantar reflexes;and hypoesthesia from D5–D9. Cerebrospinal fluid examination revealed a normal cytochemical analysis but multiple type 2 oligoclonal bands — bacteriological and mycobacterium cultures, Borrelia spp, neurotropic virus, and immunological exam were negative and neoplastic cells absent. Magnetic Resonance Imaging (MRI) of the spine showed multiple intra-axial lesions with hypersignal in T2 and contrast enhancement— suggestive of an inflammatory process. Blood work revealed the presence of antibody antiSSA (RO52), with the rest of autoimmunity tests normal – Reumathoid Arthritis, Lupus and other Autoimmune Diseases excluded – and thyroid function, vitamine B12, and folic acid were also normal. The Schirmer test was under normal values, and salivary gland biopsy confirmed the diagnosis of Sjogren Syndrome. Steroid therapy was started with Prednisone with improvement. Three months after discharge she referred weakness in the lower extremities, with no other changes in the neurological exam. MRI showed great improvement of the former lesions. An electromyogram was performed — compatible with Myopathy. Muscle biopsy revealed steroid induced myopathy, and the patient suspended Prednisone and started Azatyoprin, achieving symptom regression. Conclusion: Neurological involvement in PSS occurs in about 20% of patients, from which spinal cord involvement is by far themost frequent, aswell as themost severe. Despite being the first line of treatment, steroid therapy has many collateral effects, and isn't always tolerated.

G51D α‐synuclein mutation causes a novel Parkinsonian–pyramidal syndrome

To date, 3 rare missense mutations in the SNCA (α-synuclein) gene and the more frequent duplications or triplications of the wild-type gene are known to cause a broad array of clinical and pathological symptoms in familial Parkinson disease (PD). Here, we describe a French family with a parkinsonian-pyramidal syndrome harboring a novel heterozygous SNCA mutation. Whole exome sequencing of DNA from 3 patients in a 3-generation pedigree was used to identify a new PD-associated mutation in SNCA. Clinical and pathological features of the patients were analyzed. The cytotoxic effects of the mutant and wild-type proteins were assessed by analytical ultracentrifugation, thioflavin T binding, transmission electron microscopy, cell viability assay, and caspase-3 activation. We identified a novel SNCA G51D (c.152 G>A) mutation that cosegregated with the disease and was absent from controls. G51D was associated with an unusual PD phenotype characterized by early disease onset, moderate response to levodopa, rapid progression leading to loss of autonomy and death within a few years, marked pyramidal signs including bilateral extensor plantar reflexes, occasionally spasticity, and frequently psychiatric symptoms. Pathological lesions predominated in the basal ganglia and the pyramidal tracts and included fine, diffuse cytoplasmic inclusions containing phospho-α-synuclein in superficial layers of the cerebral cortex, including the entorhinal cortex. Functional studies showed that G51D α-synuclein oligomerizes more slowly and its fibrils are more toxic than those of the wild-type protein. We have identified a novel SNCA G51D mutation that causes a form of PD with unusual clinical, neuropathological, and biochemical features.

Teaching Neuro Images : Cerebral adrenoleukodystrophy

A 42-year-old man with Addison disease presented to the emergency department with unsteady gait for 1 year. A half-brother had epilepsy and difficulty walking, and died at 6 years of age. Another half-brother has a longstanding gait disorder. Over 3 to 4 months, his gait has become worse with marked stiffness, ataxia, and dysarthria. Neurologic examination demonstrated saccadic pursuit, ocular flutter, severe spasticity throughout, peripheral neuropathy, hyperreflexia, clonus, with bilateral extensor plantar reflexes, marked dysmetria, and dysdiadochokinesia. He stands with a marked forward stoop and flexed knees. MRI is shown in figures 1 and 2. The plasma concentration of very-long-chain fatty acids, which is a general test for peroxisomal disorders, was elevated, confirming the diagnosis of adrenoleukodystrophy (ALD). Very-long-chain fatty acids were also elevated in the surviving brother's plasma. Adult cerebral ALD is extremely rare. It is an X-linked peroxisomal disorder caused by mutation in the ABCD1 gene located at Xq28 and involves the nervous system, adrenal cortex, and Leydig cells in the testes.1,2

Extra axial adult cerebellopontine angle medulloblastoma: An extremely rare site of tumor with metastasis

Dear Sir, Medulloblastomas are rarely seen in the adult population, accounting to less than 1% of primary adult brain tumors.[6] It commonly arises from the cerebellar vermis.[5,6] There are only a few cases of cerebellopontine (CP) angle medulloblastomas. Most of them are intra-axial. Extra-axial site of this tumor is extremely rare.[2] Ours is the first case of metastasis from CP angle medulloblastoma. A 22-year-old male patient presented with headache, vomiting, ataxia, and left facial weakness of one-month duration. Vision was normal. Fundus examination showed papilloedema. He had left lower motor neuron facial paresis, left IX and X cranial nerve paresis, and left cerebellar signs. Computed tomography scan of the brain showed a left CP angle mixed-density nonenhancing lesion (5.4 × 2.8 cm) with broad-based tentorial attachment and displacement of the fourth ventricle causing obstructive hydrocephalus [Figure 1]. Findings were confirmed by magnetic resonance imaging (MRI) [Figure 2]. He had previously undergone right ventriculo peritoneal shunt for obstructive hydrocephalus elsewhere. He underwent left retromastoid craniectomy and gross total excision of the lesion. There was clear plane between the tumor and cerebellum, whereas it was adherent to tent laterally. Histopathology showed a highly cellular tumor composed of rosettes of small round cells, with high nucleus-cytoplasm ratio and increased mitotic figures—suggestive of classical medulloblastoma—WHO grade IV [Figure 3]. Postoperatively, he improved. He was advised craniospinal radiotherapy which he failed to receive and presented 15 months later with progressive quadriparesis and sensory impairment of five-month duration with bladder and bowel involvement. On examination, he had 3/5 motor power in the upper limbs and 2/5 in lower limbs and sensory impairment below D4 dermatome. All deep tendon reflexes were brisk with bilateral extensor plantar reflexes. All superficial reflexes were absent. MRI of the brain and spine showed recurrent left CP angle medulloblastoma and intramedullary lesion at cervical level and intradural extramedullary lesion at sacral level, suggestive of drop metastasis in the spine from CP angle medulloblastoma [Figure 4]. Figure 1 Contrast Computed tomography scan of the brain axial and coronal reconstruction showed a left CP angle mixed-density nonenhancing lesion with broad-based tentorial attachment Figure 2 MRI of the brain axial T1, T2 and coronal sections showed a left CP angle lesion with broad-based tentorial attachment Figure 3 Microphotograph of the histopathology slide. (H and E, ×20). showed a highly cellular tumor composed of rosettes of small round cells, with high nucleus-cytoplasm ratio —suggestive of medulloblastoma Figure 4 Saggital MRI of the cervical and sacral region showing drop metastasis (shown by arrows) Medulloblastoma usually occur in inferior medullary velum in the midline.[6] However, rarely they may occur laterally in the cerebellar hemisphere in adults.[3] Origin of medulloblastoma may be either from germinal cells or their remnants situated at the end of posterior medullary velum or from remnants of the external granular layer.[5,7] Their development in the CPA may be from the remnants of the external granular layer in the cerebellar hemisphere, including the flocculus which faces the CP angle.[5] In CP angle medulloblastomas, though fifth, sixth, and eighth cranial nerves are frequently involved,[4] these nerves were spared in this patient. CP angle medulloblastomas are rare with nearly 35 cases published in the literature,[2,5] of which only 9 are in adults.[2,5] The lack of association with any cerebellar tissue and extra-axial location in the region of CP angle is an extremely rare phenomenon.[2] Medulloblastomas are known to metastasize through CSF to the spinal canal, leptomeninges, and supratentorial regions. Metastasis in medulloblastomas vary between 38 and 60% in various series,[1,6] with the spinal canal being the commonest site with approximately 58%.[6] Kumar et al. have reported a case of vermian medulloblastoma with metastasis to the CP angle.[5] To the best of authors’ knowledge, spinal metastasis from CP angle medulloblastoma has not been reported till date. Extra-axial site of this tumor is extremely rare but must be considered in the differential diagnosis of extra-axial CP angle lesions. Any neurological deterioration seen in follow-up patient must be evaluated for metastasis.

Leukaemic alveolar rhabdomyosarcoma

A 13-year-old previously well girl presented with a five-week history of lethargy, loss of weight and left upper quadrant pain radiating to her thoracolumbar spine. Examination revealed pallor, left upper quadrant tenderness and bilateral lower limb weakness with brisk lower limb and extensor plantar reflexes together with bilateral clonus. Peripheral blood counts showed pancytopenia: haemoglobin concentration 70 g/l, platelet count 70 · 10/l and neutrophil count 0AE8 · 10/l, and a blood film was leucoerythroblastic. She was in acute renal failure and her lactate dehydrogenase, calcium and urate were elevated at 1886 u/l (230–600), 2AE84 mmol/l (2AE15–2AE65) and 925 umol/l (150–330), respectively. Chest and spine radiographs were normal, as was abdominal ultrasonography. A bone marrow aspirate demonstrated an infiltrate of large cells with prominent nucleoli and basophilic cytoplasm with multiple vacuoles (top left). Flow cytometric analysis showed these cells to be CD56/CD45 (top right). Whole body magnetic resonance imaging revealed a diffusely abnormal bone marrow signal throughout the axial skeleton and a soft tissue lesion centred on T9/T10 with an epidural extension compressing the spinal cord (bottom right). Urinary catecholamines were negative. A T9-10 laminectomy/biopsy yielded a histological diagnosis of alveolar rhabdomyosarcoma with desmin, vimentin, myogenin and myoD1 positivity together with fluorescence in situ hybridization confirmation of the PAX3-FOXO1 fusion gene (bottom left). Immediate treatment with hyperhydration, rasburicase and dexamethasone restored normal renal function and calcium levels. Chemotherapy with ifosfamide/vincristine/actinomycin-D/doxorubicin produced an excellent clinical and tumour response. Rhabdomyosarcoma, especially of alveolar histology has a propensity to metastasize to the bone marrow. Not infrequently, rhabdomyoblasts are mistaken for the blast cells of acute leukaemia. Immunophenotyping usually shows these cells to be CD56/CD45 and they express desmin, vimentin, myoglobin and MyoD1. The cytogenetic hallmarks are the translocations t(2;13)(q35;q14)/PAX3-FOXO1 and t(1;13) (p36;q14)/PAX7-FOXO1, seen in approximately 60% and 20% of cases respectively.

Neurological disorders in HIV-infected children in India

There are few studies of HIV-related neurological disorders from centres in low-income countries where facilities are available for detailed investigation. Records of all patients attending the paediatric HIV outpatient department at B. J. Wadia Hospital for Children, Mumbai between April 2000 and March 2008 were reviewed. Of 668 HIV-infected patients, 48 (7.2%) had neurological manifestations and are included in this study. Twenty-six (54.2%) children had HIV encephalopathy. Other causes of neurological manifestations include febrile convulsion in five (10.4%), bacterial meningitis in three (6.3%), epilepsy in two (4.2%), tuberculous meningitis and progressive multi-focal encephalopathy in two (4.2%) each and toxoplasmosis, vasculitis, acute demyelinating encephalomyelitis, anti-phospholipid antibody syndrome, Down's syndrome, birth asphyxia, herpes simplex encephalopathy and mitochondrial encephalopathy in one (2.1%) each. Mean (SD) age at presentation was 4.36 (3.38) years with a range of 2 months to 15 years. The common subtle neurological manifestations were abnormal deep tendon reflexes and extensor plantar reflexes. The common symptomatic manifestations were delayed milestones in 21 children (43.8%) and seizures in 19 (39.6%). Seizures were more common in males (54%) than in females (25%) (p=0.038). In children <5 years, delayed milestones was the most common manifestation while focal neurological deficits were more common in older children. Of the 13 children who received HAART, nine (60.23%) improved. Early diagnosis of neurological disorders in HIV-infected children is important for appropriate investigation and management, especially the introduction of HAART.

Clinical Reasoning: A 35-year-old man with a right hemiplegia and a cerebral mass

A 35-year-old man presented with progressive right face, arm, and leg weakness, and diffuse headache. He lived in rural northwest Argentina. He had a past medical history of sexually transmitted diseases. On examination, he was alert and fully oriented, and had a right hemiparesis with hyperreflexia and an extensor plantar reflex. Apart from low grade fever, the rest of the physical examination was unremarkable. The complete blood count revealed leukopenia (3,300 leukocytes/mL); renal function, liver tests, electrolytes, erythrocyte sedimentation rate, and glucose level were normal. He tested positive for HIV with a CD4 count of 18 cells/mm3 and viral load of 133,400 copies/mm3. Brain CT showed a nonenhancing left temporoparietal lesion with surrounding edema and midline shift. ### Questions for consideration: The patient was started on empirical treatment for toxoplasmosis without clinical improvement. A brain MRI with gadolinium performed days later showed a left temporoparietal mass with a ring-like enhancement pattern and marked perilesional edema (figure). Serologies for hepatitis B virus, hepatitis C virus, VDRL, and Toxoplasma (immunoglobulin G, immunoglobulin M, and immunoglobulin A subtypes) were negative. Blood cultures for bacteria, fungi, and mycobacteria were also negative. Since the patient lived in an endemic area, a search for Chagas disease was performed. The serology confirmed chronic Chagas disease (both indirect immunofluorescence and indirect …

Early Neurologic Abnormalities Associated with Human T-Cell Lymphotropic Virus Type 1 Infection in a Cohort of Peruvian Children

Because human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) may occur in some children infected with HTLV-1, we sought to determine the prevalence of neurologic abnormalities and any associations of neurologic abnormalities with infective dermatitis in these children. We enrolled 58 children infected with HTLV-1 and 42 uninfected children (ages 3 to 17) of mothers infected with HTLV-1 in a family study in Lima, Peru. We obtained medical and developmental histories, surveyed current neurologic symptoms, and conducted a standardized neurologic examination without prior knowledge of HTLV-1 status. HTLV-1 infection was associated with reported symptoms of lower extremity weakness/fatigue (odds ratio [OR], 6.1; confidence interval [CI], 0.7 to 281), lumbar pain (OR, 1.7; 95% CI, 0.4 to 8), and paresthesia/dysesthesia (OR, 2.6; CI, 0.6 to 15.8). HTLV-1 infection was associated with lower-extremity hyperreflexia (OR, 3.1; CI, 0.8 to 14.2), ankle clonus (OR, 5.0; CI, 1.0 to 48.3), and extensor plantar reflex (OR undefined; P = .2). Among children infected with HTLV-1, a history of infective dermatitis was associated with weakness (OR, 2.7; CI, 0.3 to 33), lumbar pain (OR, 1.3; CI, 0.2 to 8), paresthesia/dysesthesia (OR, 2.9; CI, 0.5 to 20), and urinary disturbances (OR, 5.7; CI, 0.5 to 290). Abnormal neurologic findings were common in Peruvian children infected with HTLV-1, and several findings were co-prevalent with infective dermatitis. Pediatricians should monitor children infected with HTLV-1 for neurologic abnormalities.

Transient Corneal Edema and Left Hemisphere Dysfunction in Pearson Syndrome

Pearson syndrome is a rare mitochondrial disorder of infancy manifested by sideroblastic anemia, pancytopenia, exocrine pancreatic insufficiency, and variable involvement of the kidneys and liver (1). Large deletions in the mitochondrial genome lead to derangement of oxidative metabolism and a decreased mitochondrial energy supply (2). The neurologic manifestations include hypotonia, developmental delay, ataxia, and tremor (3). There are no reported ophthalmic findings. Patients who survive infancy may later develop Kearns-Sayre syndrome (KSS) (4). Persistent corneal edema attributed to endothelial dysfunction has been reported in KSS (3,5,6) and in chronic progressive external ophthalmoplegia (CPEO) (7), but transient corneal edema has not been reported in any mitochondrial disorder. We recently examined a 3-year-old girl with Pearson syndrome who developed transient corneal edema in conjunction with transient left cerebral hemispheric dysfunction manifesting as left gaze deviation and right hemiparesis. Such phenomena have not been reported previously in Pearson syndrome. Pearson syndrome was diagnosed in the patient at 12 months of age after she presented with transfusion-dependent sideroblastic anemia. Testing revealed a large mitochondrial DNA deletion. She later developed pancreatic insufficiency and Fanconi renal disease. At 3 years and 9 months of age she was admitted for severe sepsis due to Salmonella infection. Before this admission, she had had no known neurologic abnormalities. A normal ophthalmologic examination with a pediatric ophthalmologist had occurred 1 month before admission. She required intubation, pressor support, and chest compressions for episodes of cardiac arrest. After extubation, she exhibited lingering reduced consciousness, left gaze deviation, and right hemiparesis. She failed to respond to verbal stimuli. A right extensor plantar reflex was present. Her eyes were fully deviated to the left and did not cross the midline to command, visual stimuli, or the oculocephalic maneuver. Both corneas were cloudy. Results of dilated fundus examination were unremarkable. Brain MRI obtained during this episode showed diffuse parenchymal volume loss but was otherwise unremarkable. MRI spectroscopy was not performed. Electroencephalography showed diffuse slowing but no epileptiform activity. The hemiparesis, gaze deviation, and corneal edema had resolved within 1 week. The patient was discharged in her baseline state. Stroke-like manifestations are well documented in many mitochondrial disorders, most notably the condition called mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) (8), but not in Pearson syndrome. Reversible corneal edema has not been described in any mitochondrial disorder. We presume that in our patient this ocular manifestation, together with transient cerebral hemispheric dysfunction, were related to an exacerbation of impaired mitochondrial function triggered by the sepsis (9) Lee et al (3) described a 3-year-old girl with Pearson syndrome who was discovered to have persistent corneal haze and early retinitis pigmentosa in conjunction with acute pancreatitis. She died 4 months later without autopsy. Chang et al (5) reported the histopathologic results on the post-mortem cornea of a patient with KSS who died at age 27 and had had persistent corneal edema since age 4. It showed edema of the epithelium with areas of bullous separation, thickening of Descemet's membrane, and absence of the endothelium and Bowman's membrane. Boonstra et al (6) reported stromal and epithelial corneal edema by biomicroscopy as the initial sign of KSS in a 6-year-old boy. At age 14, biomicroscopic examination showed endothelial edema as well. Nakagawa et al (10) described improvement of corneal edema in an 11-year-old boy with KSS during treatment with antioxidants. Brain MRI performed during stroke-like episodes in MELAS typically shows transient restricted diffusion predominantly affecting gray matter (11), a feature not seen in our patient. It is possible that a later MRI would have shown abnormalities. Magnetic resonance spectroscopy or positron emission tomography, reported to show abnormalities in mitochondrial disorders in which MRI appears normal might also have marked the left hemisphere dysfunction (12,13). Anna C. Momont, MD Jonathan D. Trobe, MD Kellogg Eye Center Department of Ophthalmology and Visual Sciences University of Michigan Ann Arbor, Michigan [email protected]

Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: implications for clinical management

While Friedreich's ataxia (FRDA) and ataxia telangiectasia (AT) are known to be the two most frequent forms of autosomal recessive cerebellar ataxia (ARCA), knowledge on the other forms of ARCA has been obtained only recently, and they appear to be rarer. Little is known about the epidemiological features and the relative frequency of the ARCAs and only few data are available about the comparative features of ARCAs. We prospectively studied 102 suspected ARCA cases from Eastern France (including 95 from the Alsace region) between 2002 and 2008. The diagnostic procedure was based on a sequential strategic scheme. We examined the clinical, paraclinical and molecular features of the large cohort of patients and compared features and epidemiology according to molecular diagnosis. A molecular diagnosis could be established for 57 patients; 36 were affected with FRDA, seven with ataxia plus oculomotor apraxia type 2 (AOA2), four with AT, three with ataxia plus oculomotor apraxia type 1 (AOA1), three with Marinesco-Sjögren syndrome, two with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), one with ataxia with vitamin E deficiency (AVED) and one with autosomal recessive cerebellar ataxia type 2 (ARCA2). The group of patients with no identified mutation had a significantly lower spinocerebellar degeneration functional score corrected for disease duration (SDFS/DD ratio; p = 0.002) and comprised a significantly higher proportion of cases with onset after 20 years (p < 0.01). Extensor plantar reflexes were rarer and cerebellar atrophy was more frequent in the group of patients with a known non-Friedreich ARCA compared to all other patients (p < 0.0001 and p = 0.0003, respectively). Lower limb areflexia and electroneuromyographic evidences of peripheral neuropathy were more frequent in the Friedreich ataxia group than in the group with a known non-Friedreich ataxia and were more frequent in the later group than in the group with no identified mutation (p = 0.0001 and p = 0.01, respectively). The overall prevalence of ARCA in Alsace is 1/19,000. We can infer the prevalence of FRDA in Alsace to be 1/50,000 and infer that AT is approximately eight times less frequent than FRDA. MSS, AOA2 and ARSACS appear only slightly less frequent than AT. Despite the broad variability of severity, Friedreich ataxia patients are clinically distinct from the other forms of ARCA. Patients with no identified mutation have more often a pure cerebellar degenerative disease or a spastic ataxia phenotype. It appears that ARCA cases can be divided into two major groups of different prognosis, an early-onset group with a highly probable genetic cause and an adult-onset group with better prognosis for which a genetic cause is more difficult to prove but not excluded. ARCAs are rare, early-disabling and genetically heterogeneous diseases dominated by FRDA. Several of the recently identified ARCAs, such as AVED, ARSACS, AOA1, AOA2 and MSS, have a prevalence close to AT and should be searched for extensively irrespective of ethnic origins. The strategic scheme is a useful tool for the diagnosis of ARCAs in clinical practice.

Interobserver variation in the evaluation of neurological signs: observer dependent factors.

Interobserver variation among four observers in evaluation of eight selected neurological signs was investigated. MATERIAL & METHODS--Two hundred and two consecutive unselected inpatients were examined by two senior neurologists and two trainees, all without knowledge of the neurological case history. The signs examined were: anisocoria, jerky eye movements, facial palsy, elbow extension force, finger-nose test, Barré sign, knee jerk, and extensor plantar reflex. Observed agreement rates and kappa coefficients were calculated in order to compare the interobserver variability among neurologists and trainees, and to evaluate differences in the interobserver variability between signs. RESULTS--Observed agreement rates varied from 0.80 to 0.95 for neurologists and from 0.65 to 0.98 for trainees. For neurologists kappa coefficients ranged from 0.40 to 0.67 and for trainees from 0.22 to 0.81. The neurologists had higher kappa values than the trainees in 5 signs, but this difference was only statistically significant for jerky eye movements. For the individual signs the observed agreement rates were between 0.50 and 0.93 for all four examiners combined, and overall kappa values varied from 0.32 to 0.71 with highest agreement for facial palsy and lowest for knee jerk. CONCLUSION--The magnitude of the interobserver and intersign variation indicates that the interpretation of the neurological signs tested, without knowledge of the case history, should be done with some caution.

Chikungunya virus is a cause of encephalitis in children in bellary, India

Introduction: Chikungunya virus, a single stranded RNA Alphavirus of the family Togaviridae, is transmitted to humans by the bite of Aedes aegypti, Aedes albopictus and other mosquitoes. An epidemic starting in Reunion Islands in March 2005 spread to Southern India, affecting 1.3 million people between Oct 2005 and Oct 2006. The epidemic reached Bellary, Karnataka in southern India by Dec 2005. Methods: From Oct 2005 to Dec 2007, children admitted to the paediatric department of the Vijayanagar Institute of Medical Sciences with an acute encephalitis syndrome were prospectively studied. All children presenting to the paediatric ward were recruited if they had suspected CNS infection or acute flaccid paralysis [and] fever or history of fever in the previous 2 weeks, together with one or more of the following: meningism (neck stiffness), photophobia, severe headache meriting lumbar puncture, altered mental state, reduced consciousness, convulsions, focal neurological signs or acute flaccid paralysis. Results: 243 patients have been recruited to date. Between April and Oct 2006, 8 children had positive plasma PCR tests for Chikungunya RNA and are described in more detail. Viral RNA was also detected by PCR in the CSF of 3 of these 8. Mean age was 6 years, range 8 months to 11 years, 5 were girls. 3 children had a rash at some stage in their illness and one had conjunctivitis. Altered mental state was reported in 7, and 6 had a GCS of less than 15 at admission. One had deafness, 3 had nausea and vomiting, and 3 had meningism. 7 had seizures, amongst whom 4 had an episode of status epilepticus (seizure lasting more than 30 minutes). 3 were aphasic during their illness and 4 had extensor plantar reflexes. There were no fatalities. At discharge, 2 patients had ongoing aphasia. The remaining 4 with a reduced GCS at admission had recovered to full coma score. Sequencing information obtained from the E1 envelope gene from plasma and CSF samples confirmed that the chikungunya genomes are of the East African lineage, which appears to have caused the more severe epidemic form of illness, compared to the Asian genotype which previously circulated in India. Conclusions: Chikungunya virus causes encephalitis in children and may be found in the CSF. It can cause severe neurological disease sequelae although the extent to which these sequelae will persist is uncertain. Given frequent travel between Asia and Europe and the potential for autochtonous transmission, as has occurred in Italy, we need to be increasingly aware of global disease outbreaks. A CASE OF HYPERCALCAEMIA IN THE RETURNING

Risk factors for malignant spinal cord compression and leptomeningeal metastases in cancer patients presenting to an urgent care center

9606 Background: Malignant spinal cord compression is an oncologic emergency that is associated with considerable morbidity including irreversible loss of neurologic function. As many of the presenting signs and symptoms of spinal cord compression are common to other less-threatening conditions, it would be helpful to identify early clinical predictors specific for spinal cord compression. Methods: The medical records of all patients who presented to the emergency department of a cancer center and required spine MRI imaging in 2003 were reviewed. MRI findings were correlated with neurologic presentation. Results: There were 176 MRIs performed on 164 patients (84 men, 80 women; median age 63, range 22–96) with breast (n=31, 19%), prostate (n=29, 18%), lung (n=26, 16%), colon (n=9, 5%), myeloma (n=9, 5%), or other malignancies (60, 37%). Fifty two (29.6%) MRIs demonstrated spinal cord compression (SCC, defined as thecal sac compression with associated T2 signal change in cord) and 13 (7.4%) demonstrated incidental leptomeningeal metastases (LM). Multivariate logistical regression analysis identified four independent predictors of SCC: male gender (OR=2.95, 95% CI= 1.27–6.85, p=0.01), prior history of vertebral fracture (OR=9.09, 95% CI= 3.90–21.17, p< 0.0001), severe back pain (OR=4.21, 95% CI= 1.76–10.06, p= 0.001), and abnormal sensory exam (OR=9.45, 95%CI= 3.29–27.20, P<0.0001). SCC was noted in 13% of patients with only one risk factor and 90% of patients with 3 or more risk factors. Of note, 21 (40%) of scans demonstrating SCC were performed in patients without clinical evidence of weakness. The three independent risk factors associated with the presence of LM include: age less than 55 (OR=5.52, 95% CI= 1.40–21.7, p=0.02), extensor plantar reflex (OR=10.96, 95% CI= 2.77–43.46, p<0.001), and absence of tenderness upon palpation of spine (OR=8.02, 95% CI= 2.06- 31.23, p=0.003). Conclusions: Some of these findings are consistent with prior retrospective studies and provide a useful framework for assessing cancer patients in whom the diagnosis of SCC or LM are considered. In particular, absence of leg weakness does not exclude SCC, and the high rate of incidental LM demonstrates the importance of performing contrast enhanced scans. No significant financial relationships to disclose.

Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia

Myokymia is characterized by spontaneous, involuntary muscle fiber group contraction visible as vermiform movement of the overlying skin. Myokymia with episodic ataxia is a rare, autosomal dominant trait caused by mutations in KCNA1, encoding a voltage-gated potassium channel. In the present study, we report a family with four members affected with myokymia. Additional clinical features included motor delay initially diagnosed as cerebral palsy, worsening with febrile illness, persistent extensor plantar reflex, and absence of epilepsy or episodic ataxia. Mutation analysis revealed a novel c.676C>A substitution in the potassium channel gene KCNA1, resulting in a T226K nonconservative missense mutation in the Kv1.1 subunit in all affected individuals. Electrophysiological studies of the mutant channel expressed in Xenopus oocytes indicated a loss of function. Co-expression of WT and mutant cRNAs significantly reduced whole-oocyte current compared to expression of WT Kv1.1 alone.

Plantar reflex amusement

Every century-old truism of clinical neurology is worthy of critical review. But not every critical review is worthy. Miller and Johnston’s1 kappa statistical demise of the Babinski sign invites the prescription of C.R.A.P. (Circular Reasoning or Anti-intellectual Pomposity) detectors.2 In regard to upper motor neuron impairment (UMNI), they test the competitive reliability in the neurologic examination between elicitation of a hyperactive spinal reflex and impaired performance of a voluntary motor task. Validation is by correlation with the gold standard deficient performance of another voluntary task. The three phenomena are 1) extensor plantar reflex (Babinski sign), 2) slowed foot tapping, and 3) leg weakness. The standard physical examination is a menu with varied normative standards, some quantitative, like body temperature. For each organ/system the data range from passive anatomic/physiologic observation to active functional tests/tasks that require varying degrees of conscious cooperation. Thus for cardiac function, routine observations may include systolic and diastolic arterial pressure, recumbent and standing, pulse rate and regularity, respiratory rate, pedal edema, and auscultation sounds of turbulent flow and valvular dysfunction. But there is no simple bedside quantitative measure of cardiac …

An autosomal recessive cerebellar ataxia syndrome with upward gaze palsy, neuropathy, and seizures

The authors describe three siblings born to consanguineous parents with early onset ataxia, dysarthria, myoclonic, generalized tonic clonic seizures, upward gaze palsy, extensor plantar reflexes, sensory neuropathy, and normal cognition. Direct screening excluded mutations in FRDA, TDP1,and SACS genes and at 8344, 3243, and 8993 positions of mitochondrial DNA. Linkage analysis excluded AOA-1, EPM1, EPM2A, EPM2B, CAMOS, and recessive ataxias linked to chromosome 9q34-9qter. This clinical constellation may represent a distinct form of early onset cerebellar ataxia.

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Fibroelastoma of the mitral valve–a curable cause of stroke

A 39-year-old healthy male chemical engineer, with no significant previous medical history, presented at our hospital with sudden onset (over a period of 4 h) of dysphasia, agraphia, mild right hand hemiparesis, and asterognosis. On admission, we did a neurological examination which showed mild attention impairment, anterograde amnesia, mild conduction aphasia, and impairment of right-left discrimination. Somatic motor examination revealed a right pyramidal syndrome with brachial hemiparesis and extensor plantar reflex on the right.