Thirteen-month-old girl with hyporegenerative macrocytic anemia due to Brown-Vialetto-Van Laere syndrome 2.

We diagnosed a 13-month-old girl with severe neurological deficits and hyporegenerative macrocytic anemiawith Brown-Vialetto-Van Laere syndrome type 2 (BVVL 2), a rare disorder of the riboflavin transporter, caused by variants in the SLC52A2 gene. Bone marrow aspiration revealed hypoplastic erythropoiesis and vacuolization of myelocytes, proerythroblasts, and micromegakaryocytes. We suggest BVVL 2 as an important differential diagnosis in hyporegenerative macrocytic anemia as rapid diagnosis and initiation of therapy are crucial for the remedy of hematological and neurological impairment.

Impact of expiratory strength training in amyotrophic lateral sclerosis.

INTRODUCTION: We evaluated the feasibility and impact of expiratory muscle strength training (EMST) on respiratory and bulbar function in persons with amyotrophic lateral sclerosis (ALS). METHODS: Twenty-five ALS patients participated in this delayed intervention open-label clinical trial. Following a lead-in period, patients completed a 5-week EMST protocol. Outcome measures included: maximum expiratory pressure (MEP); physiologic measures of swallow and cough; and penetration-aspiration scale (PAS) scores. RESULTS: Of participants who entered the active phase of the study (n = 15), EMST was well tolerated and led to significant increases in MEPs and maximum hyoid displacement during swallowing post-EMST (P < 0.05). No significant differences were observed for PAS scores or cough spirometry measures. CONCLUSIONS: EMST was feasible and well tolerated in this small cohort of ALS patients and led to improvements in expiratory force-generating pressures and swallow kinematics. Further investigation is warranted to confirm these preliminary findings. Muscle Nerve 54: 48-53, 2016.

Acute bulbar, neck and limb weakness with monospecific anti-GT1a antibody: A rare localized subtype of Guillain-Barré syndrome.

INTRODUCTION: Acute bulbar, neck, and limb weakness carries several potential differential diagnoses. Although a diagnosis can often be established clinically, investigations such as electrodiagnostic and antibody testing can provide support for the clinical diagnosis and may aid in understanding the pathogenesis. A 65-year-old woman presented with acute bulbar, neck, and rapidly progressive bilateral upper limb weakness. METHODS: Clinical evaluation, electrophysiological, and serological studies were undertaken. RESULTS: Neurophysiology demonstrated proximal conduction block. A clinical diagnosis of pharyngeal-cervical-brachial weakness, a localized variant of Guillain-Barré syndrome, was made. The patient received treatment with intravenous immunoglobulin and made a remarkable recovery over the next month. She was found to have serum monospecific anti-GT1a antibodies. CONCLUSIONS: We report a case of pharyngeal-cervical-brachial weakness with monospecific anti-GT1a antibodies and discuss the differential diagnosis of acute bulbar, neck, and limb weakness.

Anti-GQ1b antibody syndrome: anti-ganglioside complex reactivity determines clinical spectrum.

BACKGROUND AND PURPOSE: Anti-GQ1b antibodies have been found in patients with Miller Fisher syndrome as well as its related conditions. Our aim was to identify the mechanism by which autoantibodies produce various clinical presentations in 'anti-GQ1b antibody syndrome'. METHODS: Immunoglobulin G antibodies to ganglioside complex (GSC) of GQ1b or GT1a with GM1, GD1a, GD1b or GT1b were tested in sera from patients with anti-GQ1b (n = 708) or anti-GT1a (n = 696) IgG antibodies. Optical densities of the single anti-GQ1b or anti-GT1a antibodies were used as reference (100%), and those of anti-GSC antibodies were expressed in percentages to reference. The relationships between anti-GSC antibody reactivity and the corresponding clinical features were assessed by multivariate logistic regression analysis. RESULTS: Ophthalmoplegia and hypersomnolence were significantly associated with complex-attenuated anti-GQ1b and anti-GT1a antibodies. Ataxia was associated with GD1b- and GT1b-enhanced anti-GQ1b antibodies or GM1-enhanced anti-GT1a antibodies. Bulbar palsy was associated with GT1b-enhanced anti-GQ1b antibodies. Neck weakness was associated with GD1a-enhanced anti-GQ1b antibodies. Arm weakness was associated with GD1b-enhanced anti-GQ1b and GD1a-enhanced anti-GT1a antibodies. Leg weakness was associated with GD1a-enhanced anti-GQ1b and anti-GT1a antibodies. CONCLUSIONS: Differences in fine specificity of anti-GQ1b antibodies are associated with clinical features, possibly due to the different expression of gangliosides in different parts of the nervous system.

Auditory neuropathy in Brown-Vialetto-Van Laere syndrome due to riboflavin transporter RFVT2 deficiency.

AIM: Mutations in the genes encoding the riboflavin transporters RFVT2 and RFVT3 have been identified in Brown-Vialetto-Van Laere syndrome, a neurodegenerative disorder characterized by hearing loss and pontobulbar palsy. Treatment with riboflavin has been shown to benefit individuals with the phenotype of RFVT2 deficiency. Understanding the characteristics of hearing loss in riboflavin transporter deficiency would enable early diagnosis and therapy. METHOD: We performed hearing assessments in seven children (from four families) with RFVT2 deficiency and reviewed results from previous assessments. Assessments were repeated after 12 months and 24 months of riboflavin therapy and after cochlear implantation in one individual. RESULTS: Hearing loss in these individuals was due to auditory neuropathy spectrum disorder (ANSD). Hearing loss was identified between 3 years and 8 years of age and progressed rapidly. Hearing aids were not beneficial. Riboflavin therapy resulted in improvement of hearing thresholds during the first year of treatment in those with recent-onset hearing loss. Cochlear implantation resulted in a significant improvement in speech perception in one individual. INTERPRETATION: Riboflavin transporter deficiency should be considered in all children presenting with an auditory neuropathy. Speech perception in children with ANSD due to RFVT2 deficiency may be significantly improved by cochlear implantation.

Concomitant rheumatoid arthritis and amyotrophic lateral sclerosis: report of two new cases and review of literature.

To describe a rare association between rheumatoid arthritis (RA) and amyotrophic lateral sclerosis (ALS). Two new cases of patients with RA who developed amyotrophic lateral sclerosis (ALS), one receiving anti-TNFα agents, were reported. Only other five cases of this rare association have been previously described in literature. The simultaneous presence of the two diseases represents a difficult diagnostic challenge because RA may mimic some musculoskeletal symptoms of ALS. There is no evidence in favor of a common pathophysiologic mechanism, and thus the possibility of a fortuitous association must be raised. A neurotoxic side effect of various drugs for RA treatment could be considered. Casual or causal association remains a difficult choice. The possibility of a coincidental association must be raised but neurologic side effects of TNFα blockers lead to discussion.

Refractory bulbar and respiratory dysfunction in a young Chinese woman with seronegative, muscle-specific tyrosine kinase antibody-positive myasthenia gravis: response to cyclophosphamide and rituximab treatment.

The use of cyclophosphamide and rituximab for patients with refractory myasthenia gravis has shown promising results. We report on a 31-year-old Chinese woman with acetylcholine receptor antibody-negative and muscle-specific tyrosine kinase antibody-positive generalised myasthenia gravis who had refractory bulbar dysfunction and respiratory failure despite immunosuppressive therapy and thymectomy, and partial and sustained responses to cyclophosphamide and rituximab treatment, respectively. Myasthenia crisis was diagnosed when she presented in the third trimester of pregnancy with dysphagia, bilateral ptosis, prominent fatigability, and respiratory failure. She required prolonged intensive care and non-invasive ventilatory support despite several courses of intravenous immunoglobulins and plasmapheresis. Pulse cyclophosphamide 500 mg/m(2) was given monthly for 4 consecutive months with a partial response. Rituximab 500 mg weekly was subsequently given for 4 weeks with a dramatic and sustained response. She remained symptom-free and assumed full maternal care at 1 year. To the authors' knowledge, this is the first report of a Chinese patient with refractory myasthenia gravis who responded to cyclophosphamide and rituximab.

Thyrotoxicosis presenting as acute bulbar palsy.

Myopathy chiefly affecting the proximal muscles of the limbs is frequently seen in hyperthyroidism. But isolated acute bulbar palsy without skeletal muscle involvement is rare in thyrotoxicosis. We report the case of a 52 year old man who presented with severe dysphagia, dysphonia and bouts of aspiration. Laboratory testing revealed an underlying Graves' thyrotoxicosis. His symptoms recovered dramatically within 6 weeks with treatment of hyperthyroidism. This case is reported to emphasize that thyrotoxicosis should be considered in the differential diagnosis of dysphagia of obscure etiology.

Isolated bulbar paralysis in a patient with medullar tau pathology: a case report.

Increased morbidity and mortality rates as well as some other manifestations in Alzheimer's disease can be explained by subcortical degeneration. Pathological evidence is scarce but confirmative. We report a 77-year-old patient who presented with a 6-year history of dyspnoea, stridor and dysphagia. Unexpectedly, histopathological examination disclosed extensive degeneration of the medulla by tau pathology. The majority of symptoms and signs could be explained by the medullary tau pathology. Whether the medullary tau pathology in this case was a rare aberrant progression of Alzheimer's disease or a new presentation of tauopathy concomitant with subclinical Alzheimer's disease should be elucidated by additional studies.

[Acupuncture at pharyngeal acupoints for true bulbar paralysis after cerebral infarction: a randomized controlled trial].

OBJECTIVE: To compare the clinical effect of acupuncture at the affected side and both sides of the pharyngeal acupoints for true bulbar paralysis after cerebral infarction. METHODS: A total of 66 patients with true bulbar paralysis after cerebral infarction were randomly divided into an unilateral group and a bilateral group, 33 cases in each group, 1 case dropped off in each group at last. On the basis of conventional drugs and electro-nape-acupuncture treatment, the patients in the unilateral group were treated with acupuncture at the affected side's Tunyan, Fayin and Zhifanliu (Extra), while patients in the bilateral group were treated with acupuncture at the both sides' Tunyan, Fayin and Zhifanliu. The treatment was performed once a day, 6 days a week, and the clinical effect was assessed after 21-day therapy. The swallowing and vocalization of the two groups were evaluated by dysphagia grading scale, Kubota water swallowing test and GRBAS grading scale before and after treatment. RESULTS: After 21 days of treatment, the scores of the dysphagia grading scale in the two groups were both improved (P<0.01), and the unilateral group was superior to the bilateral group (P<0.01). The GRBAS grading scale and Kubota water swallowing test grading after treatment were improved in both groups (P<0.01), and the unilateral group was superior to the bilateral group (P<0.05, P<0.01). CONCLUSION: Acupuncture at the pharyngeal acupoints of the affected side achieves much better therapeutic effect on true bulbar paralysis as compared with the acupoints of the bilateral sides.

Automated Acoustic Analysis of Oral Diadochokinesis to Assess Bulbar Motor Involvement in Amyotrophic Lateral Sclerosis.

Purpose The purpose of this article was to validate a novel acoustic analysis of oral diadochokinesis (DDK) in assessing bulbar motor involvement in amyotrophic lateral sclerosis (ALS). Method An automated acoustic DDK analysis was developed, which filtered out the voice features and extracted the envelope of the acoustic waveform reflecting the temporal pattern of syllable repetitions during an oral DDK task (i.e., repetitions of /tɑ/ at the maximum rate on 1 breath). Cycle-to-cycle temporal variability (cTV) of envelope fluctuations and syllable repetition rate (sylRate) were derived from the envelope and validated against 2 kinematic measures, which are tongue movement jitter (movJitter) and alternating tongue movement rate (AMR) during the DDK task, in 16 individuals with bulbar ALS and 18 healthy controls. After the validation, cTV, sylRate, movJitter, and AMR, along with an established clinical speech measure, that is, speaking rate (SR), were compared in their ability to (a) differentiate individuals with ALS from healthy controls and (b) detect early-stage bulbar declines in ALS. Results cTV and sylRate were significantly correlated with movJitter and AMR, respectively, across individuals with ALS and healthy controls, confirming the validity of the acoustic DDK analysis in extracting the temporal DDK pattern. Among all the acoustic and kinematic DDK measures, cTV showed the highest diagnostic accuracy (i.e., 0.87) with 80% sensitivity and 94% specificity in differentiating individuals with ALS from healthy controls, which outperformed the SR measure. Moreover, cTV showed a large increase during the early disease stage, which preceded the decline of SR. Conclusions This study provided preliminary validation of a novel automated acoustic DDK analysis in extracting a useful measure, namely, cTV, for early detection of bulbar ALS. This analysis overcame a major barrier in the existing acoustic DDK analysis, which is continuous voicing between syllables that interferes with syllable structures. This approach has potential clinical applications as a novel bulbar assessment.

Thrombectomy and reconstruction of the left vertebral artery after total arch replacement: never give up on postoperative stroke.

The patient was a 64-year-old man who had aortic regurgitation, ischemic heart disease, a transverse aortic aneurysm, and an abdominal-common iliac aneurysm. Concomitant operations including aortic valve replacement, coronary artery bypass grafting, and total aortic arch replacement with elephant trunk technique were performed successfully. The patient developed postoperative cardiac tamponade on the 5th postoperative day, resulting in bulbar palsy due to occlusion of the dominant left vertebral artery. Thrombectomy of the vertebral artery with reconstruction by a saphenous vein was performed. The patient's neurological symptoms improved after the operation. Revascularization of ischemic stroke may yield neurological improvement even in patients after cardiovascular surgery.

Radiation-induced cranial neuropathies manifesting as baroreflex failure and progressive bulbar impairment.

INTRODUCTION: Baroreflex failure and bulbar palsy have been rarely reported as potential complications of radiotherapy for head and neck tumors. However, the occurrence of both disorders in the same patient has not been well described. We present a unique patient with radiation-induced cranial neuropathies, resulting in bulbar palsy and baroreflex failure. CASE REPORT: A 67-year-old man underwent surgical resection of tonsillar squamous cell carcinoma and postoperative radiation therapy. Six years later, he developed severe orthostatic hypotension with syncope, followed later by progressive bulbar impairment. EMG showed myokymic discharges in the tongue, and marked orthostatic hypotension was noted on tilt-table testing. CONCLUSION: Progressive bulbar impairment and baroreflex failure can occur following radiotherapy for head and neck cancers. Furthermore, these manifestations of radiation injury can occur in the same patient.

Secondary hypokalemic paralysis with bulbar weakness and reversible electrophysiologic abnormalities: A case report and systematic review.

Hypokalemic periodic paralysis secondary to distal renal tubular acidosis presenting with prominent bulbar symptoms is extremely rare. The exact pathophysiology by which hypokalemia causes weakness is yet to be elucidated though muscle and nerve membrane hyperpolarization have been hypothesized. The pathophysiology of bulbar involvement in this condition is even more unclear. We report a case presenting as acute flaccid quadriplegia with prominent bulbar symptoms that reversed once potassium levels returned to normal. Serial nerve conduction studies were performed at various potassium levels revealing electrophysiologic abnormalities that corrected with potassium repletion. A systematic review of the literature was also conducted focusing on bulbar symptoms and electrophysiologic findings in hypokalemic periodic paralysis. Nerve conduction abnormalities in this condition are seldom documented, but reports have shown reduced amplitudes of compound motor action potentials and abnormal F-waves during acute attacks of hypokalemic paralysis.

[An elderly case of Guillain-Barré syndrome with anti-GT1b antibodies].

An 85-year-old Japanese female was admitted with sudden onset of quadriparesis with areflexia. Preceding infection was not present. IgG anti-GT1b antibodies were prominently positive in serum. Nerve conduction study results suggested Guillain-Barré syndrome (GBS) classified as acute motor sensory axonal neuropathy (AMSAN). While intravenous immunoglobulin (IVIg) was started, bulbar palsy and respiratory failure progressed and the condition deteriorated. Although mechanical ventilation was required, second IVIg course led to gradual improvement of quadriparesis and bulbar palsy. In the present case with elderly-onset disease, the levels of anti-GT1b antibodies were elevated, which is relatively rare in GBS. It was suggested that anti-GT1b antibodies may be related to the development of axonal GBS with bulbar palsy.

[A case of neuromyelitis optica spectrum disorders, with slowly progressive bulbar palsy, mimicking a motor neuron disease].

A 52-year old woman first noted dysphagia four months before admission followed by dysarthria two months later. She then developed weakness of all limbs and became unable to walk. All these symptoms, associated with tongue atrophy, slowly progressed, leading to the initial clinical impression of a motor neuron disease, although her nerve conduction study and electromyography showed no abnormalities. Her brain MRI with T2 weighted/diffusion weighted image (DWI)/fluid attenuated inversion recovery (FLAIR) revealed a high signal lesion located at dorsal medulla oblongata. She proved positive for anti-aquaporin 4 antibody, which confirmed the diagnosis of neuromyelitis optica spectrum disorders (NMOSD). We conclude that NMOSD may initially present with progressive bulbar palsy and pyramidal tract disorder over a few months, mimicking a motor neuron disease. Awareness of this atypical presentation helps establish an early diagnosis of this treatable entity.

Hypophonia as only presenting symptom in myasthenia gravis - a diagnostic dilemma in poor countries: a case report.

INTRODUCTION: The autoimmune disease myasthenia gravis can mimic a variety of neurological disorders leading to a delay in diagnosis and treatment. In the older population, due to confusion with signs of the ageing process or comorbidities due to ageing, there are many underdiagnosed or misdiagnosed cases of myasthenia gravis. A majority of myasthenia gravis symptoms appear as ocular or motor symptoms and there are very few cases of bulbar symptoms. We present a case of myasthenia gravis with only hypophonia as a clinical feature. CASE PRESENTATION: We present a case of a 51-year-old Madheshi woman whose only complaint was sudden onset of hypophonia which later showed a fluctuating nature throughout the daytime. There was only reduced pitch in her voice with no nasal tone or dysarthria (so-called dysphonia), which created a diagnostic dilemma. Later, a neurological examination and other relevant investigations suggested myasthenia gravis. CONCLUSIONS: Sudden onset and focal neurological deficit can raise the diagnostic dilemma of myasthenia gravis. Relevant laboratory tests and clinical examinations are important to diagnose this disease properly. In resources-deprived nations like Nepal, where several investigations are expensive and access to them is difficult, it becomes very difficult to achieve a solid diagnosis for rare presentations of diseases.

Upper aerodigestive tract sequelae in severe enterovirus 71 infection: predictors and outcome.

OBJECTIVE: 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. PATIENTS AND METHODS: 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 age <2 years, body weight <10th 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. RESULTS: Significant tracheostomy and gastrostomy predictors were age <2 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. CONCLUSIONS: 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.