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Introduction Acute liver porphyrias are caused by mutations of genes encoding the heme biosynthesis enzymes. A lack of any of these enzymes leads to a decrease in the heme level, which in each case is manifested by identical clinical symptoms. Nervous tissue is particularly susceptible to a depletion of heme levels. Three classical symptoms of a porphyria attack include: abdominal pain (as a manifestation of autonomic neuropathy), peripheral neuropathy, and psychic disturbances. Apart from the main symptoms, porphyria attacks may be manifested as various neurological disturbances, such as: bulbar palsy, epileptic seizures, psychic disturbances and focal symptoms of CNS damage. The intensity of individual symptoms can vary. Although neurological symptoms usually disappear after the attack, they may cause permanent deficits. Through involving CNS, porphyria can mimic other neurological disorders. Damage to the nervous system can be confirmed by additional examinations. Thus far, disseminated focal changes during the attack, which disappear after the regression of clinical symptoms, have been described in magnetic resonance imaging (MRI) scans of the brain. Spinal cord abnormalities in MRI scans have not been described yet, despite the fact that damage to the anterior horn associated with porphyria has been confirmed in literature. While examining cerebrospinal fluid during the attack, an elevated protein level has been noticed, so far without the presence of oligoclonal bands. Aim This paper aimed to demonstrate that porphyria should be considered in differential diagnosis of clinically isolated syndrome (CIS) and multiple sclerosis (MS). Materials and Methods This paper is based on the case of a symptomatic patient who carried a mutation in one of the genes for porphyria, and who developed a clinical manifestation of focal damage to CNS. A differential diagnosis of porphyria and CIS, with a subsequent conversion to a clinically defined MS, was carried out. The results of additional examinations performed routinely in both disorders, the clinical picture and data from medical literature have been used in the analysis of this case. Case study The authors present the case of a patient with confirmed genetic porphyria, who was hospitalized for purposes of establishing a diagnosis due to weakened lower extremities. The patient manifested spastic lower extremity paresis, sensation disorders and urinary incontinence, which indicated spinal cord damages. An MRI scan of the thoracic spine revealed disseminated foci with contrast enhancement. A high level of proteins and oligoclonal bands were detected in the cerebrospinal fluid. On the basis of a new clinical picture (differing from the previous attack symptoms), prolonged symptoms, spinal cord lesions in MRI, and the presence of oligoclonal bands, CIS was diagnosed. Quick and complete recovery was obtained due to the administering of a steroid therapy. After several months, the patient reported a similar, passing episode, which, according to the authors, confirmed the diagnosis and an expected conversion to a clinically defined MS. Results and discussion Taking into consideration the clinical manifestation of spinal cord involvement untypical of porphyria, the detection of spinal lesions in an MRI scan, the presence of oligoclonal bands in the cerebrospinal fluid and the positive effect of steroid therapy, the authors believe that this described patient, who was a symptomatic carrier of a mutation in a gene for porphyria, developed CIS. Conclusions This reported case, supported by data from medical literature, shows that porphyria should be taken into consideration in any differential diagnosis of CIS and MS.

A 30-year-old healthy woman experienced speech disturbance and swallowing difficulty at two months of pregnancy. She was diagnosed as myasthenia gravis (MG) with anti-MuSK antibodies. At eight months of pregnancy, bulbar palsy, eye movement disturbance, and muscle weakness worsened unexpectedly. Plasma exchange was performed three times daily starting from the 1st day of the 37th pregnancy week (2 L/day, albumin substitution of 5%) and the patient underwent caesarean section and gave birth to the girl safely. The infant had anti-MuSK antibodies in the serum and umbilical cord blood. The infant's suckling power was weak. The infant was diagnosed as transient neonatal myasthenia gravis. There is no case where management of MG has been performed from the period of pregnancy for anti-MuSK positive patients. For the control of Anti-MuSK positive patients in addition to normal care for Anti-AChR antibodies positive patients, it is important to carefully observe symptoms caused by bulbar palsy, draw attentions on malnutrition and polyhydramnios, and perform simple plasmapheresis on regular basis without any delay.

Myeloid Sarcoma1 (also termed as chloroma, granulocytic sarcoma, extra medullary myeloid tumor) is a rare extra medullary tumor composed of immature myeloid cells (myeloblast)2. It is usually associated with leukemia or other myeloproliferative disorder. Myeloid Sarcoma in the central nervous system, around the brain stem is the commonest site of presentation and require high suspicion for diagnosis. We report a forty years male patient with history of dysphagia, dysphonia for last two months. MRI showed chloromas around the brain stem. Laboratory investigations revealed the presence of AML. This is a rare case of Myeloid Sarcoma around the brain stem in a patient of AML. DOI: http://dx.doi.org/10.3329/bjms.v13i4.16056 Bangladesh Journal of Medical Science Vol.13(4) 2014 p.481-483

Botulism is a neuroparalytic illness resulting from the action of a potent toxin produced by the organism Clostridium botulinum. It can present with a classic triad of clear mentation, bulbar palsy and symmetric descending paralysis. Treatment is symptomatic and includes a botulinum antitoxin.

Objective:To report outcomes for the first known cochlear implantation procedures in two patients with Brown–Vialetto–Van-Laere syndrome.Patients:Two adult patients (a brother and sister) with post-lingual sensorineural deafness associated with Brown–Vialetto–Van-Laere syndrome. The female patient presented with a milder form of the syndrome.Intervention:Cochlear implantation.Main outcome measure:Post-implantation speech discrimination scores.Results:Auditory evoked potential testing suggested pathological changes in both patients' cochleae, auditory nerves, brainstem and (probably) central auditory pathways. In the male patient, despite implantation of the better ear, the Bamford–Kowal–Bench sentence score was zero at 21 months post-implantation. In the female patient, Bamford–Kowal–Bench sentence scores at six months post-implantation were 25 per cent in quiet and 3 per cent in noise.Conclusion:These poor clinical outcomes appear to be related to retrocochlear and probable central auditory pathway degeneration.

A 64 year old man presented with a three week history of transient slurred speech, progressive headache, right sided weakness, ophthalmoplegia, and facial droop. Magnetic resonance imaging of the brain (fig …

Aims and Objectives: To study the incidence, clinical profile and outcome of children with diphtheritic neuropathy. Methodology: A retrospective study of 26 patients with clinical diagnosis of post diphtheritic neuropathy was done. The records were reviewed and information regarding demographic profile, immunization status, clinical presentation, treatment received (medical &/ or surgical including ventilator care) & the outcome were recorded in pro-forma. The results were tabulated and analysed. All the cases who had whitish grey adherent membrane and evidence of neck swelling or has laboratory confirmed evidence (smear or culture positive cases) were diagnosed as cases of diphtheria and amongst them who developed features of neurological deficits like bulbar palsy, cranial nerve involvement or limb weakness were enrolled for further information amongst the survived cases of diphtheria. Patients with other evident cause for neurological deficit were excluded. During this time period total 138 patients of diphtheria were admitted at our hospital and among them 38 patients expired due to various complications. Results: Incidence of Diphtheritic neuropathy was 29.8% among survived cases of diphtheria in our study. Median age of presentation was 7 years and Median latency period was 18 days. Among these patients 96% patients were either partially immunised or unimmunized. All of them had features of bulbar palsy. Isolated palatal palsy was most common presentation and was present in 53.84% patients. GBS like illness was present in 4 (15.38%) patients. Cranial nerve involvement was present in 8% of patients. Full recovery was seen in 30.7% and partial recovery was seen in 46.15% of patients. Boys were more in numbers. Conclusion: Diphtheria is a vaccine preventable disease so, routine vaccine administration, prompt diagnosis, early treatment, early administration of ADS and early recognition of complications and treatment of such will reduce associated morbidity and mortality.

Brown-Vialetto-Van Laere syndrome is a rare neurological disorder with a variable age at onset and clinical course. The key features are progressive ponto-bulbar palsy and bilateral sensorineural deafness. A complex neurological phenotype with a mixed picture of upper and lower motor neuron involvement reminiscent of amyotrophic lateral sclerosis evolves with disease progression. We identified a candidate gene, C20orf54, by studying a consanguineous family with multiple affected individuals and subsequently demonstrated that mutations in this gene were the cause of disease in other, unrelated families.

Historical studies of eye movements in motor neurone disease (MND) have been conflicting although current findings suggest that eye movement abnormalities relate to frontal lobe impairment. Numerous case reports, however, describe slow saccades and supranuclear gaze palsies in patients with MND often associated with bulbar-onset disease. We performed a study of saccades and smooth pursuit in a large group of patients with MND to examine for any differences between bulbar-onset and spinal-onset patients. Forty-four patients (14 bulbar-onset and 30 spinal-onset patients) and 45 controls were recruited. Reflexive saccades, antisaccades and smooth pursuit were examined using infra-red oculography and all subjects then underwent neuropsychological evaluation. Reflexive saccades were found to be slower in bulbar-onset compared to spinal-onset patients and controls (p = 0.03, p = 0.05). Antisaccade latency (p = 0.01) and antisaccade type 1 errors (p = 0.03, p = 0.04) were increased in patients compared to controls. 'Proportion of time spent in smooth pursuit' and smooth pursuit 'velocity gain' were reduced in patients compared to controls (p = 0.000, p = 0.001). Antisaccade errors and velocity gain correlated with neuropsychological measures sensitive to lesions of the frontal lobes. This is the first study to highlight the presence of slow saccades in bulbar-onset MND. These findings suggest that slow saccades may be due to increased brainstem pathology in bulbar-onset disease that involves burst cell neurons. Furthermore these observations highlight the potential for overlap between bulbar-onset MND and progressive supranuclear palsy (PSP) as both can have a bulbar palsy and slowed saccades.

Dysarthria is a motor disorder of speech characterized by abnormalities of the articulation and intelligibility of speech. Phonation and the rate of facial movements may also be affected. Understanding the nature and course of dysarthria in amyotrophic lateral sclerosis (ALS) is important because loss of communication prevents patients from participating in many activities, may lead to social isolation, and reduces the quality of life. The goal of management of dysarthria in ALS patients is to optimize communication effectiveness for as long as possible. The information about dysarthria in ALS is dispersed in physiological, pathological, speech therapy, otorhinolaringological and neurological publications. This review summarizes the current state of knowledge on the clinical features, differential diagnosis, pathophysiology, investigations and management of dysarthria in ALS patients. There is a need to compare the different methods used to assess dysarthria and for controlled clinical trials to assess therapeutic strategies.

Neuroimaging studies in amyotrophic lateral sclerosis (ALS) investigating movements of the hands have in general found increased activation compared to healthy controls, which has been interpreted in terms of cortical adaptation as a result of corticospinal tract damage. Here, we investigated brain activations to vertical tongue movements using functional MRI at 3 tesla. Whereas healthy controls, patients with Kennedy syndrome, and ALS patients without bulbar involvement showed robust and indistinguishable activations in pre- and postcentral areas and the thalamus, ALS patients with bulbar involvement showed a significant decrease of cortical activity and missing thalamic activity. This decrease stands in marked contrast to the increase of activity observed in ALS patients when performing limb movements. We discuss these divergent findings with regard to the different physiological properties of tongue and limb movements. These findings may also help to explain the faster time-course of the disease in patients with bulbar involvement.

Twenty patients (M:F 15:5) with electrophysiological evidence of predominant axonal lesion and fulfilling clinical criteria for Guillain Barré Syndrome were observed during a period of 6 years (1985-1990). Their mean age was 27.5 years (range 5-55). Seven patients had antecedent febrile illness. Peak motor deficit was reached at a mean period of 6.5 days (range 2-21 days). All the patients had distal muscle weakness out of proportion to proximal muscle weakness. Facial paresis (13 patients), bulbar palsy (2), respiratory failure (1), sensory deficits (7) and dysautonomia (1) were other salient features. CSF analysis revealed albumino-cytological dissociation in 12 patients. One patient died and in the remaining patients the recovery was delayed and incomplete. Presence of predominant distal muscle wasting and weakness, low amplitude CMAP or inexcitable nerves, absence of conduction block or significant temporal dispersion, normal or only slightly reduced conduction velocity and evidence of poor recovery suggest that the primary pathology in these patients may be axonal degeneration. These cases may represent a distinct entity and need to be differentiated from the more commonly observed acute idiopathic demyelinating neuropathy.

Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease caused by a CAG repeat expansion in the androgen receptor gene. Because the progression of SBMA is slow, it is plausible to identify biomarkers that monitor disease course for therapeutic development. To verify whether the 6-min walk test (6MWT) is a biomarker of SBMA, we performed the 6MWT in 35 genetically confirmed patients and in 29 age-matched healthy controls. The walk distance covered within 6 min (6MWD) was significantly less in SBMA than it was in controls (323.3 +/- 143.9 m and 637.6 +/- 94.2 m, respectively; P < 0.001). In test-retest analysis, the intraclass correlation coefficient for the 6MWD was high in SBMA patients (r = 0.982). In a 1-year follow-up the 6MWD significantly decreased at a rate of 11.3% per year. Our observations suggest that the 6MWT is a biomarker that can be used to monitor progression of motor impairment in SBMA.

We describe a 52-year-old man with body weight loss and bulbar palsy, who exhibited muscle atrophy and weakness with fasciculation especially in the respiratory muscles 4 years prior to death, necessitating respiratory support for 4 years, but who was able to walk until the end-stage. He had no significant family history. Neuropathological examination revealed severe loss of motor neurons in the spinal cord and brainstem, and ubiquitin-positive skein-like inclusions and Bunina bodies in the remaining neurons. In addition, prominent degeneration of the anterolateral funiculus and severe loss of neurons in the intermediate zone of the spinal cord were evident, without marked alteration of the corticospinal tracts. Degeneration of the subthalamic nucleus, increased iron deposition in the substantia nigra, and axonal swelling, residual nodules and acidophilic granules in the spinal ganglia were found. The patient's condition was considered to have been a forme fruste or incipient form of widespread-type amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND) with pallido-nigro-luysian atrophy (PNLA). The neuropathological features of the present case appear to be important for understanding the nature of widespread-type ALS and MND with PNLA.

Sialorrhea (drooling or excessive salivation) is a common problem in patients with progressive neurolomuscular diseases and bulbar palsy. Contributing factors are hypersecretion of saliva induced by cholinergic drugs and poor dental status. Non-invasive ventilation is often severely impaired in these patients. Treatment should be initiated with a thorough evaluation of the medication and of the oral status by an otorhinolaryngologist. As drooling is commonly caused by poor oral or pharyngeal neuromuscular control, swallowing therapy should be initiated by a speech therapist. Further treatment options are anticholinergic medications, botulinum toxin injections into the salivary gland, radiation and and surgical procedures. Whereas systemic anticholinergic medications lead often to side effects, the (ultrasound-guided) injection of botulinum toxin into the parotid and submandibular gland is a safe and effective method for controlling drooling for at least 2 months.

Enterovirus 71 (EV71) infection sequelae can be severe and life-threatening, and long-term follow-up outcomes remain unknown. Therefore, we conducted a retrospective follow-up study to review airway and neurological sequelae development in patients with severe EV71 infection. We also studied the incidence and risk factors for tracheotomy and gastrostomy requirement.We investigated 202 EV71-infected children according to their disease stage. Seventy-two of them were diagnosed to have EV71 encephalitis, which was characterized by myoclonus, ataxia, nystagmus, oculomotor palsy and bulbar palsy or combinations of these conditions. All the 72 patients required endotracheal intubation due to respiratory failure or ventilator dependence; among these, 14 underwent tracheostomy and 10 underwent gastrostomy. All patients were followed-up for at least 3 years after discharge. Predictors of tracheostomy and gastrostomy requirement were age2 years, body weight10th percentile, pulmonary hemorrhage or edema, meningeal symptoms and magnetic resonance imaging (MRI) findings of upper spinal cord and brainstem. We determined outcome based on persistent tracheostomy or gastrostomy requirement and whether patients developed positive neurological sequelae.Significant tracheostomy and gastrostomy predictors were age2 years, pulmonary edema or hemorrhage, hypotension, hemiparesis and positive MRI findings. Statistical analysis revealed pulmonary edema and hypotension as index predictors of tracheostomy requirement and pulmonary edema as the significant risk factor for gastrostomy.Long-term neuropsychological impact was observed on children who present the signs of the pulmonary edema or hypotension in the early onset of the EV71 infection. EV71-infected patients who develop neurological pulmonary edema or hypotension should be hemodynamically stabilized and undergo early tracheostomy to prevent further complications. This may improve the decannulation success rate after the brainstem function recovers.

The clinical status and daily-life activity of 136 patients with amyotrophic lateral sclerosis (ALS) living in Nagano prefecture were evaluated. The mean age of the patients was 67.4 ± 10.4 years, and the mean age at onset was 61.0 ± 12.3 years. Thirty-nine patients (29.1%)developed the disease after 70 years of age. The mean duration of disease was 6.5 years (maximum 41 years), and 26 patients showed a duration of disease of over 10 years. Sixteen of these patients did not need artificial nutritional or respiratory support. Sixty-seven patients (49.3%) needed total support for dressing and 54 (39.7%) for walking/moving. Forty-nine (36.3%) were unable to speak, and 49 (36.0%)needed tube feeding. Sixty-six (48.5%)had respiratory difficulties, and 34 needed mechanical ventilation. Only 27 patients (19.9 %)were almost independent. Out of 133 patients, 99 (74.4%)lived in their own home, with the remainder being hospitalized or institutionalized. Of the 34 patients requiring mechanical ventilation, 19 (55.9 %) lived in their own home, 12 were hospitalized, and 3 were institutionalized. A tendency of late-onset for ALS patients, which has been recently reported worldwide, was confirmed in Nagano. There were a significant number of ALS patients who had not developed bulbar palsy or respiratory failure regardless of duration of disease. As expected, artificial respiratory support was a major factor in the confinement of ALS patients to hospitals or nursing institutions., Article, 信州医学雑誌 55(4): 181-190(2007)

Riluzole is to date the only treatment that prolongs amyotrophic lateral sclerosis (ALS) survival. However, results on the efficacy of riluzole in observational population-based studies with a longer follow-up are conflicting and it is still unclear if the effect of the drug is limited to an early stage of the disease and to some specific subgroups of patients. The objective is: (i) to evaluate the effect of riluzole on ALS survival in a cohort of incident cases; (ii) to examine whether bulbar-ALS benefits from the medication to a greater extent and (iii) to assess the efficacy of the drug in elderly patients. Source of the study was a prospective population-based registry of ALS established in Puglia, Southern Italy. We examined survival of 126/130 incident ALS cases diagnosed during the period 1998-1999. Seventy-three patients were prescribed riluzole and the remaining 53 were not. Riluzole therapy increased survival rates at 12 months by approximately 10% and prolonged survival by 6 months (18.2 months vs. 12.4; peto-test: 2.78; P = 0.09). This beneficial effect was present amongst bulbar-onset ALS (peto-test: 4.11; P = 0.042), but not in subjects with limb-onset (peto-test: 0.48; P = 0.4). In patients aged >70 years riluzole treatment was associated with an 8 months longer median survival time [15.4 months vs. 7.1] and a reduction in mortality rate at 12 months by 27%, regardless of site of symptoms onset. In multivariate analysis, riluzole use was an independent predictor of survival at 12 months from the diagnosis with borderline significance (P = 0.06). Riluzole was effective amongst cases with bulbar-onset ALS (P = 0.04), whereas in subjects with limb-onset there was no effect on survival at 12 months (P = 0.5). In each model riluzole did not influence survival at 24 months. Conversely, riluzole use was associated with an improvement in survival amongst elderly patients both at 12 (P = 0.07), at 24 months (P = 0.03) and in the entire follow-up period (P < 0.04). In this population-based series, we found that riluzole therapy improves ALS survival. The efficacy of the drug was present amongst bulbar-onset ALS and older patients, but not in subjects with limb-onset. The favourable effect of the drug was transient, as it was lost in prolonged follow-up. Our observations support the use of riluzole at an early stage of ALS in bulbar and elderly patients. However, the appropriate duration of riluzole treatment remains to be established.

There are, certainly, similarities between Worster-Drought and congenital bilateral perisylvian syndromes, and it may be that, if not entirely the same, there is a continuum between the two. There does seem to be some confusion in the literature and a better option could be to abandon both these terms and include them under the heading of suprabulbar paresis: congenital and acquired.

A 21-year-old man presented with aspergilloma in the prepontine cistern that developed after treatment for cerebellar hematoma following rupture of an arteriovenous malformation. He became bedridden with neurological signs of tetraparesis, disturbed ocular movement, and bulbar palsy, despite alert consciousness. Repeat magnetic resonance imaging 1 year later revealed a space-occupying lesion in the prepontine cistern along the clivus. This multilobular enhanced mass lesion gradually enlarged towards the brainstem over the following 4 years, resulting in loss of spontaneous breathing and dependence on a mechanical respirator. Surgical treatment via a lateral suboccipital approach was selected to reduce the size of the mass lesion and confirm the diagnosis. Histological examination revealed the presence of Aspergillus fumigatus. Treatment with amphotericin B (1 mg/kg/day) and fluconazole (100 mg/kg/day) injected into the peripheral veins was initiated, but was stopped due to the appearance of renal dysfunction. An Ommaya tube was then inserted into the prepontine cistern via a transsylvian approach to provide high concentrations of amphotericin B around the granulomatous lesion. He gradually improved, corresponding to the decreased size of the aspergilloma just after surgery. Surgical reduction of granuloma combined with local administration of antifungal agent is a good treatment option in patients with aspergilloma refractory to systemic administration.

Thirteen patients with severe neuroparalytic snake envenomation admitted in intensive care unit with respiratory failure over a four months period. Initially ptosis and ophthalmoplegia, followed by bulbar palsy and respiratory muscle weakness was the common sequele. All of them received cardio-respiratory support with mechanical ventilation, anti-snake venom (median dose of 20 vials) and anticholinesterase therapy. Except one suffering from hypoxic brain injury due to delayed presentation, rest survived with complete neurological recovery. So good outcome in such cases is related with early cardio respiratory support and anti venom therapy

We report two patients with spinocerebellar ataxia (SCA) with cranial and spinal motor neuron involvement. They initially presented with cerebellar ataxia, followed by bulbar palsy and limb motor neuron sign. One of the patients had a brother with allied disorder. SCA type 1 (SCA1), SCA3 and SCA6 have been reported to involve the motor neuron system, but they were excluded by DNA analyses in the present two patients. These two patients may form a distinct disease entity among SCAs.

Ophthalmoplegia can occur in both Miller Fisher syndrome (MFS) and Guillain-Barre syndrome (GBS) with typical limb involvement. However, ophthalmoplegic GBS (OGBS) has been poorly defined. We aimed to characterize OGBS and clarify the pathophysiological implications across the overall GBS spectrum. Twenty GBS and seven MFS patients from three university based teaching hospitals in Korea were enrolled and analyzed. Six GBS patients who were classified as OGBS commonly also had facial diplegia (50%) and bulbar palsy (50%), while only a small portion of non-ophthalmoplegic GBS (NOGBS) patients had facial diplegia (21%). None of the patients had bulbar palsy in the NOGBS or MFS groups. The most frequent anti-ganglioside antibody in OGBS was the IgG anti-GT1a antibody (50%). The IgG anti-GM1 antibody was found mainly in NOGBS (57%) with high concordance with the pure motor type classification on electrophysiology. IgG anti-GQ1b antibody was positive uniquely in MFS (100%), although some patients were also positive for anti-GT1a antibody (71%). OGBS had distinct clinical features, including bulbar palsy, as well as ophthalmoplegia and limb weakness for both GBS and MFS. Relevant immunological factors were anti-GT1a antibody. Whether OGBS is an independent entity or a transitional spectrum remains to be established and further study will be needed.

This chapter will discuss the major divisions of the hindbrain namely the pons, medulla oblongata and the cerebellum. In addition, the details of the cell types in the cerebellum will be given, including what the afferent and efferent input is to each layer. The tracts which pass through the medulla oblongata will be summarized, but discussed in more detail in the relevant chapters later. Also, a brief section on pathology will discuss the anatomical and clinical presentation of bulbar palsy, affecting the glossopharyngeal, vagus, accessory and hypoglossal nerves. Although mentioned in this section due to their origins here, the trigeminal, abducent, facial, vestibulocochlear, glossopharyngeal, vagus, accessory and hypoglossal nerves have already been discussed in detail in Chapter 1.

We report here an autopsy case of neuro-Behcet's disease. The patient was a 28-year-old man, who developed a slight fever, right uveitis, and right sensory neural hearing loss at the age of 25. These symptoms relapsed repeatedly despite treatment. Eventually he was admitted to hospital because of progressing neurological deficits such as pyramidal symptoms, somatic sensorial and autonomic disorders, and bulbar palsy. The patient's condition deteriorated and he died of heart failure. Total clinical course was about three years. In postmortem examination, various-sized necrotic foci, often accompanied by gliosis and foamy macrophage infiltration, were scattered in the diencephalic region and brain stem. Meningitis was observed on the ventral side of the brain stem as well as inferior cerebral surface. Nonbacterial or non-fungal acute perivascular inflammatory foci were also present in the brain stem and cerebellar parenchyma. These histopathological findings suggest that a destructive multifocal neutrophilic inflammation might have caused the neurological deficits. Perivascular inflammation might be important to understanding the pathogenesis of neuro-Behcet's disease.

Objective: This study was performed to evaluate which factors influence the outcome of Guillain–Barre Syndrome (GBS), focusing on the choice of treatments. Methods: Sixty-three GBS patients were retrospectively studied and the following factors were evaluated: sex, age, days from onset of disease to the start of treatment, severity of symptoms, prior infection, autonomic dysfunction, bulbar palsy, anti-ganglioside antibody, and disease form, as well as the choice of treatment. Plasma adsorption (PA, n = 39), plasma exchange (PE, n = 14), or immunoglobulin treatment (IVIg, n = 10) were performed in this study. Outcomes were evaluated using the functional grading scale (FGS) of Hughes. Results: The number of days needed for one functional grade improvement was significantly longer in the elderly, the severe symptom group, and patients with acute motor axonal form, and days needed for two functional grade improvement was significantly longer in the elderly, patients with autonomic dysfunction, and acute motor axonal form. The choice of treatments (PA, PE, or IVIg) did not significantly influence the outcome as determined by both univariate and multivariate analysis. Conclusion: Although patient age, symptoms, and disease form influenced the outcome, treatment methods did not significantly influence the outcome. Since PA does not result in a risk of unknown infection, choosing a PA treatment may be justified, especially for patients (or doctors) who may be anxious about a possibility of unknown infection.

Study objectives: To analyze (1) the impact of a protocol of early respiratory evaluation of the indications for home mechanical ventilation (HMV) in patients with amyotrophic lateral sclerosis (ALS), and (2) the effects of the protocol and of bulbar involvement on the survival of patients receiving noninvasive ventilation (NIV). Design and setting: Retrospective study in a tertiary care referral center. Patients: HMV was indicated in 86 patients with ALS, with 22 patients (25%) presenting with intolerance to treatment associated with bulbar involvement. Treatment with HMV had been initiated in 15 of 64 patients prior to initiating the protocol (group A) and in the remaining 49 patients after protocol initiation (group B). Results: In group A, the majority of patients began treatment with HMV during an acute episode requiring ICU admission (p 0.001) and tracheal ventilation (p 0.025), with a lower percentage of patients beginning HMV treatment without respiratory insufficiency (p 0.013). No significant differences in survival rates were found between groups A and B among patients treated with NIV. Greater survival was observed in group B (p 0.03) when patients with bulbar involvement were excluded (96%). Patients without bulbar involvement at the start of therapy with NIV presented a significantly better survival rate (p 0.03). Multivariate analysis showed bulbar involvement to be an independent prognostic factor for survival (relative risk, 1.6; 95% confidence interval, 1.01 to 2.54; p 0.04). No significant differences in survival were observed between patients with bulbar involvement following treatment with NIV and those with intolerance, except for the subgroup of patients who began NIV treatment with hypercapnia (p 0.0002). Conclusions: Early systematic respiratory evaluation in patients with ALS is necessary to improve the results of HMV. Further studies are required to confirm the benefits of NIV treatment in patients with bulbar involvement, especially in the early stages. (CHEST 2005; 127:2132–2138)

An update of the endemic parkinsonism-dementia complex (PDC) frequently associated with amyotrophic lateral sclerosis (ALS) in the high prevalence ALS focus of the Kii peninsula of Japan is presented. The initial symptom was parkinsonian gait or hypobulia/amnesia, which was followed by akinesia, rigidity, occasional tremor, bradyphrenia, abulia and amnesia, and finally by akinetic mutism. In several years, most of the patients developed ALS symptoms such as muscle atrophy, bulbar palsy, and upper motor neuron signs. Magnetic resonance imaging and computed tomography of the brain showed marked atrophy of the temporal and frontal lobes and the cerebral blood flow reduction on single-photon emission computed tomography. Marked loss of nerve cells associated with abundant neurofibrillar tangles (NFTs) in the entire central nervous system, most predominantly in the brainstem and temporal lobe was characteristic. Concomitant ALS pathology involving the upper and lower motor neurons was common, and senile plaques were absent in most cases. NFTs consisted of twisted tubules on electron microscopy. Western blot of tau protein showed three bands consisting of six tau isoforms, similar to those of Alzheimer's disease. A family history of ALS/PDC was recorded in more than 70% of patients, but no abnormal mutation or polymorphism was found in the genes of SOD1, tau, and apolipoprotein E. Familial nature and continuing morbidity of Kii ALS/PDC suggest that genetic factors may be more likely in its pathogenesis.

We report a paraneoplastic neuropathy with severe motor involvement following sensory-ataxic disturbance. Anti-disialosyl immunoglobulin M (IgM) antibody was detected in the course of malignant lymphoma of diffuse large B-cell type, which usually spares the motor system. Onset was subacute, with relapsing and remitting sensory ataxia, muscle weakness, bulbar palsy, respiratory paralysis, and ophthalmoplegia; only neck rotation was retained in the terminal stage. Autopsy showed no lymphoma cells infiltrating the nervous system. Motor neurons survived in the spinal cord, but mean diameter of the ventral spinal nerve roots was reduced considerably. The gracile fasciculus and the sural nerve were more markedly degenerated than proximal portions. Morphometric study showed that most of the proximal motor and sensory axons did not extend distally. This autopsy report provides further definition of a neuropathy associated with malignant lymphoma and IgM antibodies against disialosyl residues.

Diethylene glycol (DEG) is a well-known metabolic and renal toxin usually ingested accidentally as an ethanol substitute or as a contaminant in various medicinals. To date, most poisonings have occurred in third-world countries where early death from renal failure is very common. We report a series of seven patients presenting with epidemic DEG poisoning from a correctional facility with varying degrees of metabolic acidemia and acute renal impairment responding to emergent hemodialysis (HD). Significantly, three patients developed delayed neurologic toxicity which has not been well characterized in the past.Seven male patients (age range 19-55) presented over a 36 h period following ingestion of varying quantities of DEG. Initially three patients, ingesting the largest quantities of DEG, presented more than 24 h postingestion with severe metabolic acidemia (pH range 6.8-7.1) and anuric acute renal failure requiring HD. All three remained dialysis-dependent and developed significant cranial neuropathies with bulbar palsy in the second week postingestion. One patient died with cerebral oedema and a progressive encephalopathy. Two further patients presented within 24 h of ingestion with normal renal function and a moderate metabolic acidemia (pH range 7.2-7.28) requiring HD. They remained well. Finally, two further patients presented with a history of trivial DEG ingestion and did not require any therapy. Neurologic signs in the two surviving initial presenters improved over 4-6 months although they remained dialysis-dependent.Unrecognized DEG poisoning may present with metabolic acidemia and anuric acute renal failure. Established renal impairment may predict subsequent delayed neurologic toxicity.

Speech disturbance observed in patients with amyotrophic lateral sclerosis (ALS) usually arises from bulbar palsy. In those patients, atrophy and fasciculation of the tongue are observed and dysphagia might be complicated with speech disturbance in parallel. We herein describe an unusual woman with ALS whose initial symptom was apraxia of speech (AOS). A right-handed 66-year-old woman presented with a speech problem lasting for 6 months. She went to a dental clinic, departments of otolaryngology and neurosurgery at other hospitals, and a psychological clinic, but there was no abnormality detected in their examination. She was unable to speak or vocalize at all when she came to our hospital. There was no neurological disease in her family. Her parents were not consanguineous. She was alert and could walk by herself. There was no weakness of her face. Atrophy and fasciculation of the tongue was not observed. She did not complain of dysphagia. She could eat and drink anything without difficulty. There was no weakness in any of her limbs. Tendon reflexes were evoked normally. No pathological reflex was elicited. Sensory function and coordination were also normal. She could understand what we said. She could obey written commands. Although she could not speak, she could write what she wanted to say. Laryngoscopy and brain magnetic resonance imaging results were normal. Electromyography did not show any denervation potentials in muscles including the tongue. Single-photon emission computed tomography (SPECT) using I-N-isopropyl-P-iodoamphetamine revealed hypoperfusion at the middle and lower parts of the left precentral gyrus when analyzed with easy Z-score imaging system (Fig. 1) [1]. No objective examination indicated ALS at that time. One year after we had seen her for the first time, she came to our hospital requiring re-examination. There was no facial palsy, but forced laughing was observed. Atrophy and fasciculation of the tongue was seen. She did not complain of dysphagia. There was a weakness of her left lower limb. Tendon reflexes including jaw jerk were increased. Babinski sign was evoked bilaterally. The grammar of her sentences and morphology of her handwritten letters including kana (Japanese syllabograms) and kanji (Japanese ideograms) were almost correct. However, there was a phonological error in her handwriting (Fig. 2). Nerve conduction study showed decreased F wave frequency without conduction block. Electromyography revealed acute and chronic denervation potentials in her limbs. She was diagnosed as having ALS. In the next 3 years, she developed tetraplegia. Dysphagia, which developed slowly, required gastrostomy. Brain computed tomography 5 years after the onset showed atrophy of the medial temporal lobes but not the precentral gyri. Our patient’s initial symptom of speech problem was considered to be AOS. AOS is an impairment of motor planning and programming of speech articulation. Since K. Maeda (&) N. Ogawa R. Idehara Department of Neurology, National Hospital Organisation Higashi-ohmi General Medical Centre, 255 Gochi, Higashi-ohmi, Shiga 527-8505, Japan e-mail: maeda-kengo@shiga-hosp.jp

Brain death is irreversible loss of function of the brain including the brain stem. Many clinical conditions may mimic brain death. This is a case review of a 27 year old Bangladeshi male who complaints heaviness of tongue and slurring of speech and was diagnosed as a case of bulbar palsy and found to develop ascending flaccid paralysis of limbs, subsequently he developed respiratory failure was placed on mechanical ventilator (MV) with GCS -3 and brain stem and all spinal reflexes were absent. The MRI & CSF studies were unremarkble. He was on MV and had no spontaneous breathing. A provisional diagnosis of GBS was made with a dfferential diagnosis of Brain stem death. Patient recieved 5 cycles of plasma pheresis without any clinical change. EEG showed cerebral reactivity on tactile stimulation and external noise stimulation. 31ist day of his illness patient developed involuntary tongue movement with pupils weakly reacting to light. 37th day of his illness he opened his eyes with vocal command. His neurological recovery continued till discharge DOI: http://dx.doi.org/10.3329/bccj.v1i1.14371 Bangladesh Crit Care J March 2013; 1: 53-55

Patients with the pharyngeal-cervical-brachial variant (PCB) of Guillain-Barré syndrome (GBS) have anti-GT1a IgG with or without GQ1b reactivity, whereas those with Fisher syndrome (FS) or Bickerstaff's brainstem encephalitis (BBE) have anti-GQ1b IgG antibodies which cross-react with GT1a. The nosological relationship between these conditions has yet to be established. To investigate the relationships between each manifestation and between clinical features and the coexistence of anti-GQ1b IgG, we reviewed neurological signs present during illnesses of 140 patients who had anti-GT1a IgG. Based on our criteria, FS was diagnosed for 64 (46%) patients, GBS for 22 (16%), BBE for 14 (10%), and PCB for 6 (4%). Overlapping conditions were diagnosed for some patients: FS and GBS (5%), PCB and FS (5%), BBE and GBS (4%), and PCB and BBE (1%). Patients who initially had bulbar palsy developed not only PCB but FS or BBE. The population of anti-GT1a-positive patients frequently had ophthalmoplegia, ataxia, and areflexia, whereas the subpopulation who had anti-GT1a IgG without GQ1b reactivity frequently had preceding diarrhea as well as oropharyngeal, neck, and limb weakness. Patients with anti-GT1a IgG presented a variety of clinical conditions, indicative of a continuous clinical spectrum. A major part of this clinical variation was due to the coexistence of anti-GQ1b IgG. The presence of a common autoantibody (anti-GT1a IgG) and overlapping illnesses suggests that PCB is closely related not only to GBS but to FS and BBE as well.

A man with spinal and bulbar muscular atrophy (SBMA) had a short (CTG)n expansion in the myotonic dystrophy protein kinase gene as well as (CAG)n expansion in the androgen receptor gene in leukocytes. The patient had the characteristic clinical findings of SBMA, but none of myotonic dystrophy type 1 (DM1). All of his three children (a son and two daughters) had the DM1 phenotype with long (CTG)n expansions. The daughters also had heterozygous long (CAG)n expansions. Postmortem examination of the patient revealed the characteristic pathological changes of SBMA as well as muscle degeneration compatible with DM1. Gene analysis of the organs disclosed unstable long expansions of the (CTG)n repeats, in contrast to the stable (CAG)n expansions. We have assumed that SBMA and DM1 developed independently in our patient, but cannot exclude the possibility that interactive gene effects increased somatic instability.

A case of gliomatosis cerebri in a 27-year-old man showing various cranial nerve manifestations is described. He was diagnosed as having cranial mononeuritis multiplex (bilateral oculomotor nerve paralysis, left facial nerve paralysis, bulbar palsy manifestations, and hypoglossal nerve paralysis) and was hospitalized in the neurology department on August 1, 2000. Although he continued to visit the neurology department after discharge, his manifestations showed no improvement. He was sent to our department for brain biopsy in August 2001. A biopsy performed at the Sylvian fissure from the frontal lobe/temporal lobe cortex showed high intensity on T2-weighted and Flair magnetic resonance imaging (MRI). The pathological findings were diffuse low-grade astrocytoma infiltrating between the pia mater and the cerebral cortex. We believed that the astrocytoma spreading on the subpia mater was responsible for the various cranial nerve manifestations, and we started whole-brain irradiation (46 Gy) + interferon (IFN)-beta D.I.V. from September 2001. The pathological findings of the brain biopsy showed diffuse astrocytoma. The clinical presentation was dramatically improved after radiotherapy. It seemed that this tumor had spread along the subpia mater and subependyma. When he was discharged in early December, he walked by himself. The characteristic features of this case are that no lesion in the cerebellum or brain stem was found on MRI, even though the main manifestations were cerebello-brain stem manifestations, and biopsy of the cerebral cortex revealed astrocytoma. It should be noted that the clinical manifestations of astrocytoma in some cases are dissociated from the imaging observations.

A 24-year-old female presented with one-and-a-half syndrome accompanied by vertigo and hearing loss in her left ear. She had no caloric response to 0°C ice water and her pure tone average revealed 72.5 dB. She was diagnosed with left one-and-a-half syndrome due to leftward gaze palsy, adduction OS (left eye), a horizontal right-beating nystagmus OD (right eye) on her rightward gaze, normal convergence. These symptoms were also accompanied by vertical gaze palsy, mild left peripheral facial nerve palsy, left face and body hypesthesia, bulbar palsy and cerebellar symptoms. Abnormal eye movement, bilateral vestibular disfunction and left hearing loss improved with methylprednisolone pulse therapy. All her neurological symptoms except mild facial nerve palsy had disappeared one year after onset of the disease. The site of the lesion responsible for one-and-a-half syndrome was the left medial longitudinal fasciculus (MLF), paramedian pontine reticular formation (PPRF) and abducens nucleus. The lesion responsible for vertical gaze palsy seemed to occupy a wide area of the pons.

Botulism is a muscle-paralyzing disease caused by neurotoxins (types A–G) produced by the bacteria Clostridium botulinum. Symptoms of food-borne botulism most commonly appear 12–36 h after eating contaminated food, but the earliest neurological symptoms may in some cases start abruptly. Here, we report the cases of two patients with food-borne botulism who were admitted to the neurological emergency room as candidates for intravenous thrombolysis for acute stroke.

Miller Fisher syndrome (MFS), a rare variant of Guillan-Barre syndrome, is characterized by ophthalmoplegia, ataxia, and areflexia. In addition to this classic triad, symptoms may include bulbar palsy, weakness, and sensory loss. The anti-GQ1b IgG antibody is a sensitive and specific marker for MFS; it is found in more than 90% of affected patients. We describe an unusual case of MFS that presented with dramatic bilateral proptosis and chemosis.

A 12-month-old boy with progressive cranial nerve palsies followed by ventilatory failure demanding artificial ventilation, generalized muscle weakness, and rapid progression to death at the age of 21 months is described. The patient had normal early development and also apparently normal hearing at presentation of illness but, after 6 months of the onset of the disease, hearing loss was documented by brainstem auditory evoked potentials (BAEP). Although the initial clinical and laboratory findings of this infant could fit with the diagnosis of progressive childhood bulbar palsy or Fazio-Londe (FL) disease, the subsequent appearance of hearing loss suggests that this patient represents a case of progressive bulbar palsy with perceptive deafness or Brown-Vialetto-Van Laere (BVVL) syndrome. To our knowledge, this case of BVVL syndrome with severe clinical features and rapid deterioration leading to death is the youngest one reported in the literature. Furthermore, this case emphasizes the need for repeated auditory examinations, including the performance of BAEP in all cases, especially infants and young children with progressive bulbar palsy.

A 70-year-old Japanese man with amyloid polyneuropathy associated with a Val 107 transthyretin (TTR) mutation is reported. The patient presented with carpal tunnel syndrome, cardiomyopathy, bulbar palsy, dysphonia and polyneuropathy. DNA analysis of the TTR gene revealed a point mutation responsible for substitution of valine for isoleucine at position 107 of the TTR molecule. Taken together with reports of patients with the same TTR variant, Val 107 TTR mutation is probably associated with a clinical phenotype characterized by carpal tunnel syndrome, cardiomyopathy, bulbar palsy and dysphonia. This case implies a worldwide distribution of the Val 107 TTR mutation with a common clinical phenotype, despite different ethnic background.

We present a case of a Caucasian woman aged 67 years referred with a 4-day history of sore throat, dysphagia, fever and nasal blockage. Examination revealed a swollen neck and pharyngeal pseudomembrane. A throat swab was positive on culture for Corynebacterium ulcerans, with toxin expression confirmed on PCR and Elek testing. A diagnosis of classical respiratory diphtheria was made, with subsequent confirmation of the patient's domesticated dog as the source of infection. The dog had recently been attacked by a wild badger and was being treated for an ear infection. The patient made a good recovery with intravenous antimicrobial and supportive therapy; however, she subsequently developed a diphtheritic polyneuropathy in the form of a severe bulbar palsy with frank aspiration necessitating percutaneous endoscopic gastrostomy feeding. A mild sensorimotor peripheral neuropathy was also diagnosed. The patient eventually made an almost complete recovery.

Brown-Vialetto-Van Laere syndrome (BVVLS) is a genetic condition caused by a mutation in the C20orf54 gene, which also codes for an intestinal riboflavin transporter. We report the case of a female who presented at 22 months with acute-onset stridor and generalized muscle weakness, in whom a genetic diagnosis of BVVLS was made, and whose symptoms improved on therapy with high-dose riboflavin. She had previously been developing normally and was able to walk at 11 months, then developed progressive muscle weakness at 22 months, and within 2 weeks was unable to sit without support. She also demonstrated stridor and paradoxical breathing indicating diaphragmatic weakness, and required continuous non-invasive ventilation (NIV) through a tracheostomy. After treatment with riboflavin she was able to walk unaided, and her Gross Motor Functional Classification level improved from level IV to level I, having fully regained the motor function she showed before symptom onset. There were no longer signs of diaphragmatic paralysis while on NIV, and she was able to tolerate 10-minute periods off NIV before paradoxical breathing again became apparent. We therefore recommend that in all cases suspected to be in the BVVLS or Fazio-Londe spectrum, early treatment with high-dose riboflavin must be considered.

Severe respiratory muscle paralysis and ventilatory failure is rare in chronic inflammatory demyelinating polyneuropathy (CIDP). We report a 14 year child who presented with respiratory failure, bulbar and multiple cranial nerves involvement along with bilateral phrenic nerve paralysis. He was diagnosed with CIDP after electrophysiological evaluation. He required AMBU ventilation for about 4 months (including domiciliary use), after which he recovered significantly. Along with several unusual features of CIDP, this report highlights good example of steady basic intensive care to save lives and rewarding outcome of prolonged respiratory support, provided by AMBU ventilation which is a rather primitive, but inexpensive device.

INTRODUCTION We report the first findings of functional magnetic resonance imaging of the auditory cortex in a young woman with a bilateral cochleovestibular deficit as first manifestation of Brown-Vialetto-Van Leare syndrome. The patient had no open speech discrimination, even with hearing aids, and is depending on lip reading for communication. METHODS To evaluate the possible efficiency of a cochlear implantation, we investigated hemodynamic responses within the central auditory pathways using an auditory functional magnetic resonance imaging paradigm. RESULTS Blood oxygen level-dependent correlates were detected bilaterally along the auditory pathways after exposure to intermittent clicking tone stimulation at 2 kHz. CONCLUSION These results suggest integrity of the central auditory pathways and represent a positive argument to propose a cochlear implantation with the aim to restore hearing.

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Purpose of review: With advances in next-generation gene sequencing, progress in deep phenotyping and a greater understanding of the pathogenesis of motor neuron disease, our knowledge of the progressive bulbar syndromes has significantly increased in recent years. This group of heterogeneous conditions, in which the primary disorder is focused around degeneration of the lower cranial nerves, can occur in children or adults and form a spectrum of severity, based around the common feature of bulbar dysfunction. Early genetic diagnosis may allow treatment in some bulbar syndromes. Recent findings: Brown-Vialetto-Van Laere and Fazio-Londe syndromes are the most recent childhood forms of progressive bulbar palsy to be genetically defined. The clinical phenotype of this group of childhood disorders was first reported over 120 years ago. Recently, it was demonstrated that in a third of these patients Brown-Vialetto-Van Laere is caused by mutations in the SLC52A2 and SLC52A3 genes, both of which encode riboflavin transporters. Importantly, supplementation of riboflavin can lead to significant clinical improvement if started early in the disease process. Summary: Here, we outline the clinical features, management and an update on the disease mechanisms and genetic causes of the progressive bulbar syndromes.