Progressive Bulbar Palsy Research Articles

Case of hereditary neuropathy with liability to pressure palsies presenting progressive muscular atrophy with lower motor neuron degeneration in the spinal cord and the brainstem

AbstractWe present a case of hereditary neuropathy with liability to pressure palsies developing progressive muscular atrophy, caused by the deletion of peripheral myelin protein‐22. The patient had a history of episodic peripheral nerve palsies during adolescence, and later manifested progressive bulbar palsy and muscular atrophy in all extremities in his 70s. Peripheral myelin protein‐22 is known to be expressed in Schwann cells, and its messenger ribonucleic acid is also expressed in lower motor neurons in the spinal cord and the brainstem. Therefore, the presented case suggests that the deletion of peripheral myelin protein‐22 facilitated impairment of peripheral nerves and lower motor neurons with aging and/or genetic stress, which could contribute to the pathogenesis of progressive muscular atrophy.

Corticosteroid-resistant bulbar neurosarcoidosis responsive to intravenous immunoglobulin

We report an intriguing case of corticosteroid-resistant bulbar neurosarcoidosis responding to intravenous immunoglobulin. A 37-year-old man presented with dysphagia to solids and liquids, dysphonia, fatigue and 50 lb weight loss...

Accelerated neuronal differentiation toward motor neuron lineage from human embryonic stem cell line (H9).

Motor neurons loss plays a pivotal role in the pathoetiology of various debilitating diseases such as, but not limited to, amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy, progressive bulbar palsy, pseudobulbar palsy, and spinal muscular atrophy. However, advancement in motor neuron replacement therapy has been significantly constrained by the difficulties in large-scale production at a cost-effective manner. Current methods to derive motor neuron heavily rely on biochemical stimulation, chemical biological screening, and complex physical cues. These existing methods are seriously challenged by extensive time requirements and poor yields. An innovative approach that overcomes prior hurdles and enhances the rate of successful motor neuron transplantation in patients is of critical demand. Iron, a trace element, is indispensable for the normal development and function of the central nervous system. Whether ferric ions promote neuronal differentiation and subsequently promote motor neuron lineage has never been considered. Here, we demonstrate that elevated iron concentration can drastically accelerate the differentiation of human embryonic stem cells (hESCs) toward motor neuron lineage potentially via a transferrin mediated pathway. HB9 expression in 500 nM iron-treated hESCs is approximately twofold higher than the control. Moreover, iron treatment generated more matured and functional motor neuron-like cells that are ∼1.5 times more sensitive to depolarization when compared to the control. Our methodology renders an expedited approach to harvest motor neuron-like cells for disease, traumatic injury regeneration, and drug screening.

Spontaneous complete necrosis of hepatocellular carcinoma: A case report and review of the literature.

The present study reports the case of a 68-year-old male patient who presented to Tokyo Rosai Hospital for the treatment of alcoholic liver disease. A high density was observed in liver segment S2, while a tumor, 30 mm in size, exhibiting a low density was observed in the delayed phase upon contrast-enhanced computed tomography (CT), which was performed prior to admission. The tumor appeared slightly poorly defined upon abdominal ultrasound and was observed as a 30 mm low-echoic nodule that was internally heterogeneous. A 5-mm thick contrast enhancement effect was observed in the tumor border in the vascular phase on Sonazoid contrast-enhanced ultrasonography, while a defect in the entire tumor was observed in the post-vascular phase. Dysphagia had commenced three months prior to presentation and a weight loss of ~3 kg was observed. Therefore, the patient was admitted to Tokyo Rosai Hospital due to the presence of a hepatic tumor, and to undergo a close inspection of the cause of the tumor. Upon close inspection, it was determined that the weight loss and aphagia were caused by progressive bulbar paralysis. A contrast-enhanced CT was performed on post-admission day 29 as a follow-up regarding the hepatic tumor. As a result, although no change in the tumor size was observed, the contrast enhancement in the tumor borderline had disappeared. Necrosis of the tumor was considered. However, as viable persistence of the malignant tumor could not be excluded, a hepatic left lobe excision was performed. The patient was diagnosed with hepatocellular carcinoma (HCC) based on the morphology of the cellular necrosis. In addition, occlusion due to thrombus was observed within the blood vessels passing inside the fibrous capsule. It was hypothesized that the formation of a thick fibrous capsule and occlusion due to thrombus in the feeding vessel were possibly involved as the cause of complete spontaneous necrosis. Written informed consent was obtained from the patient.

Injury of the Arcuate Fasciculus in a Patient with Progressive Bulbar Palsy: A Diffusion Tensor Tractography Study

The researchersWe report on a patient with progressive bulbar palsy (PBP) who presented with Broca’s aphasia due to injury of the left arcuate fasciculus (AF), as demonstrated on diffusion tensor tractography (DTT). A 74-yearold right handed patient with PBP and six age-matched normal subjects were recruited for this study. The patient presented with Broca’s aphasia along with typical symptoms of PBP, including dysarthria, dysphasia, and mild quadriparesis. DTT was performed at five years after symptom onset. After originating from Wernicke’s area, the left AF of the patient was discontinued at the junction between the ascending and horizontal portions. The fractional anisotropy value and tract number of the left AF were more than two standard deviations lower than those of normal subjects. In contrast, the apparent diffusion coefficient value was more than two standard deviations higher than those of normal subjects. Using the configuration and parameters of DTT, the researcherswe demonstrated injury of the left AF in a patient with PBP. The injury of the left AF in this patient appeared to coincide with Broca’s aphasia. The researchersWe recommend evaluation of the AF using DTT in patients with motor neuron disease who present with aphasia.

Variante faringo-cérvico-braquial da síndrome de Guillain-Barré: uma causa rara de disfunção bulbar aguda em crianças

AIMS: To report a case of pharyngeal-cervical-brachial variant of Guillain-Barre syndrome, which is characterized by rapidly progressive bulbar palsy with upper limb, neck and oropharyngeal involvement. It is a rare disorder in childhood and most cases have been described in adolescents. CASE DESCRIPTION: A seven year-old-boy presented with dysarthria, hoarseness, dysphagia, facial diplegia and bilateral progressive upper limb weakness. These symptoms started two weeks after a gastrointestinal infection. Nerve conduction studies were compatible with an acute demyelinating polyneuropathy in the upper extremities. Anti-ganglioside antibodies in the serum (anti-GT1a, GD1a, GQ1b) were positive and Campylobacter jejuni was isolated from stools. The patient was treated with intravenous immunoglobulin and needed ventilatory support during the first 12 days of admission. He was discharged at day 15 showing improvement of his neurological deficits. He fully recovered after eleven months of follow-up. CONCLUSIONS: Although pharyngeal-cervical-brachial variant of Guillain-Barre syndrome is uncommon in children, it should be considered in a child with acute bulbar dysfunction because a timely diagnosis allows the early institution of therapeutic measures that can be lifesaving.

59.: Clinical presentations of C9ORF72 gene associated amotrophic lateral sclerosis

This is a review of clinical characteristics of patients and their family tree with amyotrophic lateral sclerosis who are positive for the C9ORF72 gene duplication. Patients with motor neuron disease who were positive for the C9ORF72 gene duplication had their detailed history and family trees reviewed. Two patients were found to have motor neuron disease and the C9ORF72 gene duplication. One patient had a history of multiple sclerosis and the other patient presented with progressive bulbar palsy and a family history suggestive of an anticipation phenomenon. Amyotrophic lateral sclerosis associated with the C9ORF72 gene duplication presents with variable penetrance and variable clinical features. Our patient with both multiple sclerosis and amyotrophic lateral sclerosis supports the link between these two diseases and the C9ORF72 gene duplication.

Recent advances in bulbar syndromes: genetic causes and disease mechanisms.

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. 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. Here, we outline the clinical features, management and an update on the disease mechanisms and genetic causes of the progressive bulbar syndromes.

Epidemiological characteristics of motor neuron disease in Chinese patients

The epidemiology, diagnosis, and treatment of motor neuron disease (MND) in Chinese patients are ill known. A registered study of 461 MND patients was conducted across 10 facilities in 7 Chinese cities from February 2009 to March 2010. Patients were classified as amyotrophic lateral sclerosis (ALS) (84.4%), progressive bulbar palsy (PBP) (4.1%), progressive muscular atrophy (PMA) (10.4%), or primary lateral sclerosis (PLS) (0.9%). MND was predominant in men (men/women; 1.6:1.0). Mean onset age was 52.6years, with the highest incidence being observed between 51 and 60years. Notably, 26.0% of MND patients were employed in forestry, fishery, or animal husbandry industries. Ten cases (2.7%) reported family history of MND, and 54.2% exhibited cervical onset. MND was also associated with head/neck trauma. Non-invasive positive pressure ventilation was the most common supportive therapy. As a novel comprehensive report of a Chinese population, this study reveals that epidemiological characteristics of MND patients were similar to those observed in international populations. MND is age-related, male gender predominant, and may be associated with both environmental and genetic risk factors.

Brown-Vialetto-van Laere syndrome: A riboflavin responsive neuronopathy of infancy with singular features

We report the case of a previously healthy child presenting at 6 months of age with mild feeding difficulties and then developing hypotonia, progressive bulbar palsy with respiratory compromise and lower motor neuron signs, causing her to spend 4 months in the Paediatric Intensive Care Unit.Neurophysiological studies demonstrated a motor neuronopathy involving anterior horn cells and cranial nerve nuclei and abnormal brainstem auditory evoked potentials, leading to a diagnosis of Brown-Vialetto-van Laere Syndrome, confirmed by genetic testing (SLC52A3). Magnetic Resonance Imaging showed signal changes in the dorsal column of the spinal cord. She developed a coarse face and abnormal hair pattern.Sustained clinical improvement has been observed during almost 4 years of high-dose riboflavin therapy.

Adult-onset Alexander disease with an R66Q mutation in GFAP presented with severe vocal cord paralysis during sleep

Adult-onset Alexander disease (AOAD) is clinically characterized by slowly progressive bulbar palsy, pyramidal signs, spastic paresis and cerebellar ataxia with atrophy of the medulla oblongata and upper cervical cord, and the glial fibrillary acidic protein (GFAP) gene has been identified to be the causative gene for Alexander disease [3]. So far, some reports have mentioned that AOAD presents with sleep apnea [1, 4, 5, 8–10, 12], but the apnea mechanism is not sufficiently known. Here, we report an AOAD patient presented with vocal cord paralysis during sleep. This is the first report indicating that AOAD presented with vocal cord abductor paralysis, followed by the rapid progression of vocal cord dysfunction. A 61-year-old woman was admitted to our hospital because of gait disturbance over a 4-year period. She has been described as ‘‘round shouldered’’ since childhood and would snore loudly while sleeping since her early 30 s. Her family history revealed that even her mother snored loudly and died because of unknown reason at 54 years of age. The patient had a short neck and cervical kyphosis. Neurological examination revealed slurred speech, spasticities of all extremities, and bilateral extensor Babinski signs. MRI findings revealed atrophy of the upper cervical cord and medulla oblongata. Axial imaging of the medulla oblongata showed multiple T2-weighted high-intensity lesions. Her cerebral blood flow on ECD-SPECT was reported previously [7]. Mutational analysis revealed a previously reported heterozygous missense mutation at exon 1 of GFAP, c.197G[A, which involved the substitution of glutamine for arginine at the 66th codon (R66Q) (Fig. 1a) [11]. We confirmed the diagnosis of AOAD. Polysomnography revealed obstructive sleep apnea syndrome with 292 apneic episodes at night (245 obstructivetype and 47 mixed-type). Although her mean percutaneous oxygen saturation during wakefulness was 94 %, her mean saturation during sleep was 84 %. Her apnea–hypopnea index (AHI) was 52.2/h indicating severe apnea syndrome. To investigate the mechanism of her apnea, we examined her laryngeal movement during wakefulness and sleep induced by intravenous administration of diazepam [6]. Awake-laryngofiberscopy showed mild vocal cord abduction restriction during inspiration. After intravenous diazepam administration (5 mg), the vocal cords showed paradoxical movement with obstruction during inspiration. To avoid fatal outcome Electronic supplementary material The online version of this article (doi:10.1007/s00415-012-6540-4) contains supplementary material, which is available to authorized users.

Adolf Kussmaul (1822-1902), su biografía y descripciones

Adolf Kussmaul was born in Graben, close to Karlsruhe, Germany, on February 22,1822. He graduated at Heidelberg University in 1845 and he received his medical degree in 1855. He made original descriptions, such as the ophthalmoscope, the gastroscope or endoscope, and Kussmaul signs, besides the respiration named after him. He was the first to perform a thoracocenteses, peritoneal and gastric lavages. He rediscovered progressive bulbar paralysis (previously described by Guillaume Duchenne in 1861), polyarteritis nodosa (which was described by Karl von Rokitansky en 1852), dyslexia, (described by Thomas Willis in 1672) and pulsus paradoxus named after him, but that was reported by Richard Lower in 1669. During his 80 years of life, he wrote about different issues and topics (cardiology, rheumatology, endocrinology, gastroenterology, psychiatry, and neurology). Kussmaul was a student and professional without limits in his observation capacity. He preached with his own example in pursuit of science: observation, hypothesis, experimentation and analysis.

Speech synthesis technologies for individuals with vocal disabilities: Voice banking and reconstruction

In this invited paper, we overview the clinical applications of speech synthesis technologies and explain a few selected researches. We also introduce the University of Edinburgh’s new project ‘‘Voice Banking and reconstruction’’ for patients with degenerative diseases, such as motor neurone disease and Parkinson’s disease and show how speech synthesis technologies can improve the quality of life for the patients. 1.1. Speech Disorder and Impairment Speech disorders have a variety of causes. The major neurological degenerative diseases resulting in severe speech disorders include Motor Neurone Disease (MND), Parkinson’s, and Multiple Sclerosis; non-progressive conditions resulting in such disorders include Stroke and Cerebral Palsy. Speech impairment may also be caused by conditions such as cancer of the vocal cords, resulting in laryngectomy. MND, also known in the USA as Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig’s disease, is a debilitating neurological disease that results from the degeneration and death of the large motor neurones in the brain and spinal cord. This causes a worsening muscle weakness that leads to loss of mobility and difficulties with swallowing, breathing and speech production. Approximately 75% of MND patients are unable to speak by the time of their death [1]. There are four types of MNDs. Most cases of ALS and Progressive Bulbar Palsy are recorded in over 60’s. Age of onset of Primary Lateral Sclerosis is fifty years. Age of onset of Progressive Muscular Atrophy is usually under fifty years. About 100 new cases of MND are diagnosed in Scotland, U.K. each year.

The clinical course of progressive bulbar palsy

Our objective was to study the clinical course of patients diagnosed with progressive bulbar palsy (PBP). We reviewed all 392 medical records of ALS patients seen between 1 January 2000 and 31 July 2007. Patients with isolated PBP at presentation were selected and classified into those with normal EMG of the limbs (PBP-N) and those with active denervation on EMG (PBP-A). We studied the time to progression of these patients to ALS. We compared patients with PBP-N to patients with PBP-A. Fifteen patients were diagnosed with PBP-N. The remaining 17 had PBP-A. Thirteen of the 15 patients with PBP-N (87%) progressed to definite ALS. The two patients who did not progress to ALS died at 22 and 60 months, respectively. The median survival time was 35 months for the PBP-N group and 40 months for the PBP-A group (p = 0.92). Except for the rate of depression, patients with PBP-N did not differ from patients with PBP-A in the basic demographics, time of presentation, clinical course, survival and treatment received. All patients with FTD died within 40 months of onset of symptoms. In conclusion, almost all PBP patients progress to ALS regardless of the presence of upper motor signs or generalized denervation on EMG of the limbs.

Demographic characteristics of patients with motor neuron disease subject to conditions of large industrial city in West Siberia

78 patients with motor neuron disease (MND) were examined. Prevalence of MND in urban population of Novosibirsk on 2008/01/01 is 3,46 per 100 000 of population. In majority of patients amyotrophic lateral sclerosis (ALS) was revealed — 76 people (97,4%); primary lateral sclerosis was revealed in 1 case (1,3%), progressive bulbar paralysis was revealed also in 1 case (1,3%). There were 63 men (80,8%) and 15 women (19,2%) (ratio is 4,2 : 1,0). There was no people younger than 27 years for the moment when first symptoms of the disease were revealed. The major age group was 41 to 60 years (66 people — 84,6%).

Immunosuppressive treatment of patients with amyotrophic lateral sclerosis

Documented treatment for amyotrophic lateral sclerosis (ALS) is not available. Several studies have suggested an immunological etiology and an effect on the course of disease, when ALS-patients were treated with immunosuppressants. The aim of the present study was to evaluate the effect of immunosuppressive therapy in ALS-patients comparing the course of disease in treated patients and in historic controls with ALS; 21 patients were included in the study, 17 men and 4 women. Median age at admission was 54 years for men and 61 years for women. 5 had progressive bulbar palsy, 7 both upper and lower motor neuron affections and 9 progressive muscular atrophy. Patients were treated with prednisolone and azathioprine for 1 year and examined regularly; 12 were treated and followed for more than a year. No definite difference between survival in treated patients and their controls was found.

Behandlung der Sialorrhoe bei beatmeten Patienten

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.

Difficulties in diagnosing progressive bulbar paralysis (Fazio-Londe disease)

Background: Progressive bulbar paralysis of childhood is characterized by progressive cranial nerve palsies especially bilateral facial weakness, swallowing difficulties and bilateral ptosis. Fazio-Londe disease (OMIM 211500) is usually classified with spinal muscular atrophies of autosomal recessive or dominant inheritance. Resembling diseases are Vialetta-van Laere syndrome (OMIM 211530) and Madras-type motor neuron disease. Diagnosis consists of the clinical features, electromyograhic and histologic findings and the exclusion of other causes of progressive bulbar paresis.

Ben-Joshua Dying

Ben-Joshua Jaffee, a professionally trained social worker, was diagnosed with progressive bulbar palsy in December 2000. Subsequently, in April 2001 and February 2002, he sent two e-mails to the International Work Group on Death, Dying and Bereavement, a professional group of which he was a member. In these e-mails he described the course of his illness, his feelings, and how he coped with it. These powerful documents are a rare instance of the description of the course of a life-threatening illness, and the response of an observant, trained individual subject to it. Dr. Jaffee died on December 4, 2002.

Masseter Spasticity Successfully Treated with Neuroablations of the Bilateral Mandibular Nerves for a Patient with Progressive Bulbar Palsy

Masseter Spasticity Successfully Treated with Neuroablations of the Bilateral Mandibular Nerves for a Patient with Progressive Bulbar Palsy