Mild Truncal Ataxia Research Articles

Isolated Paravermal Hyperintensities in Neuronal Intranuclear Inclusion Disease.

A 69-year-old woman without a remarkable family history presented with a 5-year history of dizziness and gait difficulty. Neurologic examinations revealed saccadic eye movement and mild limb and truncal ataxia. She had tremor, hyporeflexia, and miosis. Fluid-attenuated inversion recovery images showed isolated bilateral paravermal hyperintensities1 (Figure). Skin biopsy demonstrated eosinophilic intranuclear inclusions positive for ubiquitin and p62 in the adipocytes and sweat gland cells. Expanded CGG repeats in NOTCH2NLC 2 lead to the diagnosis of neuronal intranuclear inclusion disease (NIID). Corticomedullary lesions are sometimes absent in the early stages of NIID and isolated paravermal hyperintensities can be the initial radiologic findings.

P-PN007. A case presenting with clinical and laboratory characteristics of fisher syndrome and lambert-eaten myasthenic syndrome (LEMS)

Introduction . Although Fisher syndrome and LEMS are classified into autoimmune neuromuscular diseases, we cannot find the coincidence of them in a single patient in the previous literature. Results . A 70-year-old female was admitted to our hospital because of bilateral hand numbness, double vision and unsteadiness which had developed 2 weeks. She had no history of preceding infection and/or related illness. On admission, her condition was characterized by mydriasis, extraocular muscle weakness, mild proximal muscle weakness and truncal ataxia. In addition, the tendon reflexes were absent at rest, and improved with brief exercise. Motor nerve conduction studies showed significantly low compound muscle action potentials (CMAPs) and increments of more than 200% after brief exercise (post-exercise facilitation) in several nerves. Sensory nerve conduction studies showed significantly low sensory nerve action potential (SNAPs) of median and ulnar nerves, and normal SNAPs of sural nerves. We also demonstrated the impairment of neuromuscular transmission in several muscles based on abnormal decrements in the repetitive nerve stimulation (RNS) test and abnormal jitter in the single-fiber electromyography (SFEMG). Both anti-GQ1b and GT1a ganglioside antibodies and P/Q-type voltage-gated calcium channel (VGCC) antibodies were positive in her sera. Her conditions improved spontaneously. She accomplished walking alone in six weeks, and paralysis of the eye muscles recovered in five months. Median and ulnar SNAPs returned to normal in accordance with recovery of clinical findings. On the other hand, low CMAPs with post-exercise facilitation remained after complete recovery. Positron emission tomography and gastrointestinal endoscopy did not show any malignancy. Conclusion . Some electrophysiological studies revealed the impairment of neuromuscular transmission using RNS and/or SFEMG in patients with Fisher syndrome. Also, it has been known that autoimmune neurological phenotypes are diverse among patients with P/Q-type VGCC antibodies. This may be the first case who showed clinical and laboratory characteristics of Fisher syndrome and LEMS simultaneously.

A case of infarction of the region from the declive to the tuber in the cerebellar vermis

AbstractWe report a rare case of infarction limited in the region from the declive to the tuber of the posterior lobe in the cerebellar vermis. A 47‐year‐old woman complained of dizziness with acute onset. Mild incoordination of the left upper extremity and mild truncal and gait ataxia was noted. Brain magnetic resonance imaging showed an infarct of the region from the declive to the tuber on the left side. In the posterior lobe, the region from the declive to the tuber is associated with coordination of the hands. The dorsal spinocerebellar tract and the ventral spinocerebellar tract convey unconsciousness proprioceptive signals from the trunk and leg and project to the anterior and posterior lobes in the cerebellar vermis. Symptoms in our patient indicated that the lesion of this region was related to the impairment of these two tracts and incidence of incoordination of the lateral upper extremity.

Bilateral striatal necrosis caused by a founder mitochondrial 14459G > A mutation in two independent Japanese families

Bilateral striatal necrosis (BSN) has many causes and is characterized by unique clinical and neuroradiological features. Herein, we report a clinical and genetic analysis of three BSN cases from two independent Japanese families harboring a mitochondrial DNA (mtDNA) 14459G>A mutation located in a coding region of the NADH dehydrogenase subunit 6 gene. In the first family, two male siblings from non-consanguineous parents exhibited similar phenotypes, with infantile-onset generalized dystonia. A third sporadic case involved a male patient with a comparatively milder phenotype characterized by juvenile-onset mild truncal ataxia and parkinsonism. Cerebral magnetic resonance imaging of these cases revealed abnormal signal intensities along the bilateral putaminal area and enlarged lateral ventricle anterior horns caused by caudate nuclear atrophy, particularly in the sibling pair. The sibling-pair cases shared a homoplasmic 14459G>A mutation, and the sporadic case showed heteroplasmy of the same mutation. Additionally, all three cases harbored the 14605A>G single nucleotide polymorphism, which was previously reported as a rare synonymous variation (4.3%) in a Japanese population. Plasmid sequencing revealed a genetic linkage of these two DNA substitutions, suggesting that the three patients shared a genetic founder. Although our mtDNA analysis was only accessible using leukocytes, clinical severity might be associated with homoplasmy or heteroplasmy. In summary, it is important to evaluate potential mtDNA defects in BSN cases, regardless of familial occurrence.

Ri antibody syndrome associated with an unusual neuroendocrine tumor

Introduction: We present a case of a paraneoplastic syndrome with Ri antibodies related to a large cell endocrine tumor of the lung. Case report: A 64 year old female patient was referred to our hospital with a one month history of dizziness, vertigo, nausea and gait instability. Her symptoms had a subacute onset with gradual progression, with more marked deterioration the week prior to presentation. Past medical history included a large cell endocrine lung tumor of the left upper lobe, which was diagnosed ten months prior to admission. She underwent a left thoracectomy with upper lobectomy followed by chemotherapy. Follow-up CT of chest–abdomen–pelvis had no signs of disease recurrence or metastasis. On admission she had severe truncal ataxia and was unable to sit upright in bed. Neurological examination revealed multi-directional saccades, mostly of the “square wave jerk” type, simulating opsoclonus, but lacking a continuous chaotic character. The abnormal eye movements were exacerbated during pursuit and were visible under closed eyelids. Oscilopsia was absent. Spontaneous myoclonic jerks of lower extremities were noted. An intention and posturaltremorofherhandswaspresent. BrainMRIwasunremarkable. Routine blood tests and screening for cancer markers was unrevealing. Cytology for malignant cells in the CSF was negative. Screening for onconeural antibodies revealed a high titer in both CSF and serum of Riantibodies. Shereceiveda 5 day courseofmethylprednisone(1 g daily), followed by a five day course of IVIG (0.4 mg/kg). Methylpredinisolone was tapered at a dose of 40 mg. Her symptoms gradually improved markedly and one month after treatment she was able to walk unassisted with mild residual truncal ataxia. The abnormal eye movements were no longer detectable. Subsequent whole body FDGPET revealed intense absorption in the hilar region of the left lung. Discussion: The presence of Ri antibodies is associated with the well characterized paraneoplastic syndrome of opsoclonus–myoclonus– ataxia. The abnormal eye movements of our patient were not fully consistent with opsoclonus. Additionally, to our knowledge, this syndrome has not been previously associated with a large cell endocrine tumor. Thus, this case report suggests that the Ri antibody syndrome can have a broader clinical phenotype and underlying etiology than previously considered. Prompt initiation of immunotherapy can result in substantial improvement of neurological deficit.

Exome sequencing reveals a novel MRE11 mutation in a patient with progressive myoclonic ataxia

Progressive myoclonic ataxia (PMA) is a clinical syndrome defined as progressive ataxia and myoclonus and infrequent seizures in the absence of progressive dementia. Due to the extremely heterogeneous nature of PMA, a large proportion of PMA cases remain molecularly undiagnosed. The aim of this study was to clarify the molecular etiology of PMA. The patient was a 52-year-old female from consanguineous parents. She developed a jerking neck movement at age 9, which gradually expanded to her entire body. On physical examination at age 47, she exhibited generalized, spontaneous myoclonus that occurred continuously. She also presented with mild limb and truncal ataxia. An electroencephalogram revealed no abnormalities. A brain MRI displayed no atrophy of the cerebellum. Electrophysiological studies suggested myoclonus of a subcortical origin. For further evaluation, we performed exome sequencing, and we identified a novel homozygous missense mutation in the MRE11 gene (NM_005590:c.140C>T:p.A47V). Subsequently, we analyzed the expression of MRE11 and related proteins (RAD50 and NBS1) via Western blot, and they were markedly decreased compared to a healthy control. Mutations in the MRE11 gene have been known to cause an ataxia–telangiectasia-like (ATLD) disorder. Accumulating evidence has indicated that its wide phenotypic variations in ATLD correspond to genotypic differences. Interestingly, our case exhibited a relatively mild decrease in NBS1 compared to previously reported cases of a homozygous missense mutation, which may account for the milder phenotype in this patient. Moreover, together with a recently reported case of an MRE11 mutation, it is suggested that MRE11 mutations can present as PMA.

Pearls & Oy-sters: A stroke of luck

An 82-year-old woman presented to the emergency room 14 hours following the onset of headache and gait unsteadiness. Twelve hours after the symptoms began, she developed left facial droop and dysarthria. The facial droop and dysarthria had resolved prior to her evaluation in the emergency room, but the gait unsteadiness and headache persisted. She had no pain aside from the mild frontal headache. Hyperlipidemia was her only identified stroke risk factor. Vital signs on admission included a blood pressure of 124/47 mm Hg and heart rate of 70 beats per minute. No murmurs were appreciated on cardiac auscultation, and pulses were symmetric. Complete neurologic examination revealed only mild truncal ataxia. She …

A Case of Cerebellar Cognitive Affective Syndrome Exhibiting Paragraphia

Paragraphia due to cerebellar cognitive affective syndrome (CCAS) has not been reported previously. This report presents a patient with cerebellar hemorrhage, showing cognitive dysfunctions including paragraphia. A 74-year-old right-handed man was hospitalized with sudden dizziness. CT demonstrated a small hemorrhage in the right cerebellar dentate nucleus. He also exhibited gait disturbance due to mild truncal ataxia and became aware of errors while writing his dairy. Neuropsychological assessments showed phonological paragraphia with Kana characters and semantic paragraphia with Kanji characters, as well as mild auditory comprehension and verbal memory disorders. Although MRI did not detect any abnormality in the cerebral hemispheres, SPECT demonstrated decreased cerebral blood flow in the left angular gyrus, frontal lobe and parieto-occipital lobe, predominantly on the left side. On neuropsychological assessment 3 months after stroke, the patient's paragraphia and auditory comprehension disorder had subsided, but his verbal memory disturbance remained. The clinical features in this case differed from those of CCAS cases previously reported. In particular, the lesion considered responsible for the cognitive dysfunctions in this case involved the right dentate nucleus, which is supplied by the superior cerebellar artery, but not the posterior inferior cerebellar artery, and especially the presence of dis-orders in writing ability, such as paragraphia. The possible mechanism of paragraphia in this case might be a reduction of cerebral blood flow in the angular gyrus due to a crossed cerebello-cerebral diaschisis. However, this case suggests that the right dentate nucleus contributes to the neuropsychological mechanism of writing.

高度の嚥下障害を呈したボレリア脳幹脳炎の１例

We report the case of a 30-year-old man who developed severe dysphagia owing to neuroborreliosis. He showed dysphagia, diplopia, hiccups, and walking difficulty Neurological examination revealed mild disturbance of consciousness, diplopia on left lateral gaze, left-side-dominant blephaloptosis, gaze-evoked horizontal nystagmus on left lateral gaze, mild bilateral muscle weakness, palatoplegia, dysphagia, dysarthria, and truncal ataxia An increased pharyngeal reflex caused dysphagia in this patient. An EEG revealed intermittent high amplitude slow wave activity. However, head MRI, blood count, serum chemistry, and cerebrospinal fluid examination showed no abnormality. Initially, brainstem encephalitis with unknown etiology was diagnosed. The hiccups, diplopia, and ptosis were improved by corticosteroid therapy, but other symptoms were refractory to corticosteroid therapy and IVIg. After these immunotherapies, anti-Borrelia IgG and IgM antibodies were found to be positive, and symptoms, including dysphagia, were improved by doxycycline and cefotaxime. Because the clinical symptoms of Borrelia infection are widely variable, neuroborreliosis should be considered in patients with brainstem encephalitis refractory to conventional immunotherapies.

Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated With Congenital Hydrocephalus in a Dog

A 13-month-old, male bichon frise was examined for the investigation of intermittent seizures, ataxia, abnormal behavior, polyuria, and polydipsia. At presentation, clinical and neurological examinations were unremarkable with the exception of mild truncal ataxia and a domed skull. Severe hyponatremia and hypoosmolality were identified, and following diagnostic testing a diagnosis of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was made. Magnetic resonance imaging revealed changes consistent with severe hydrocephalus. Water restriction resulted in increased serum osmolality and a reduction in severity of clinical signs. The current case report documents SIADH associated with hydrocephalus in a dog. Structural brain disease should be excluded before a diagnosis of idiopathic SIADH is made.

Truncal Ataxia, Hypotonia, and Motor Delay With Isolated Rhombencephalosynapsis

We report on a 16-month-old girl with developmental motor delay, microcephaly, and mild truncal ataxia who was revealed to have rhombencephalosynapsis on magnetic resonance imaging. The child was nonsyndromic and exhibited normal cognitive and social abilities for her age, despite neuroimaging findings. As this case demonstrates, motor skills in children with isolated rhombencephalosynapsis may be relatively mildly affected, and cognition may be normal despite the presence of a major central nervous system anomaly. Neuroimaging may be helpful in defining the nature of a child's deficits at an early age, particularly when associated with microcephaly and abnormalities on neurologic examination.

A Case of Intracranial Hypoglossal Neurinoma Without Hypoglossal Nerve Palsy: Operative View of the Preserved Rostral Trunk

Hypoglossal neurinomas usually manifest with hemiatrophy and weakness of the tongue. A rare case of intracranial hypoglossal neurinoma without preoperative hypoglossal nerve dysfunction and its operative view are presented. A 36-year-old female who presented with headaches and vertigo was admitted to our hospital. The neurological examination revealed bilateral papilledema and mild truncal ataxia, although weakness and atrophy of the tongue were not observed. Magnetic resonance and computed tomography images demonstrated a large foramen magnum tumor without enlargement of the hypoglossal canal. Total removal of the tumor was performed via a lateral suboccipital craniotomy and C1 partial laminectomy. During the operation, two trunks were observed for the hypoglossal nerve at the entrance of the hypoglossal canal. The tumor arose from the caudal trunk, while the intact rostral trunk entered the hypoglossal canal normally. The tumor only developed intracranially, and since the rostral trunk of the hypoglossal nerve was intact, the patient did not present with hypoglossal nerve palsy preoperatively.

Postmalaria Neurologic Syndrome: A Case Report

Neurologic signs and symptoms are common in acute malarial infection. However, after the parasites have been cleared from the blood and patients recover full consciousness, neurologic or psychiatric symptoms may occur or recur within 2 months after the acute illness. This phenomenon is called "postmalaria neurologic syndrome" (PMNS). We present a 50-year-old man who returned from the Republic of Malawi and soon developed Plasmodium falciparum malaria. Cerebral malaria, renal failure, hepatic failure, diffuse intravascular coagulation with thrombocytopenia, and upper gastrointestinal bleeding were noted during the acute stage. He was admitted to the infectious diseases ward and treated for 3 weeks. He was free from clinical general symptoms and parasites in blood smear when discharged. However, 2 weeks after discharge, he began to experience severe headache, dizziness, diplopia, mild hand tremor, unsteady gait, and easy falling. When readmitted to the neurologic ward, he presented with irritability, delirium, visual hallucination, and strange behavior. Neurologic examination was normal except for mild general weakness and evident truncal ataxia when walking. Brain magnetic resonance imaging revealed no structural lesions, and electroencephalography showed diffuse cortical dysfunction. Cerebral spinal fluid profile exhibited cytoalbuminologic dissociation. Brain single photon emission computed tomography showed diffuse cerebral parenchymal disorder. Nerve conduction studies revealed early sensory predominant polyneuropathy. The unsteadiness persisted for the initial 2 weeks of hospitalization until corticosteroid was administered. Intravenous methylprednisolone (80 mg/day) was continued for 3 days, followed by oral prednisolone (45 mg/day). His unsteadiness improved gradually after medication, and he absconded from the hospital on the 9th day of corticosteroid treatment with clear consciousness and free ambulation. The manifestation of PMNS is diverse and may present as an acute confusional state or psychosis, generalized seizure, fine tremors, cerebellar syndromes, postural hypotension, or malarial polyneuritis. Although the neurologic syndrome is primarily self-limited in most cases, corticosteroid may be beneficial in reversing PMNS.

Acute oropharyngeal palsy associated with anti-GM1b IgG antibody

Sirs: Although patients with Guillain-Barre syndrome (GBS) typically show generalized muscle weakness with areflexia, a few patients have only regional weakness throughout the disease course. O’Leary et al. [4] described three patients who had rapid progression of localized oropharyngeal weakness with or without ataxia. Unlike typical GBS or Fisher syndrome, these patients never developed limb weakness, ophthalmoplegia, or ptosis; they were regarded as having a regional variant of GBS based on detection of anti-GQ1 b and anti-GT1 a IgG antibodies in serum. Another patient with acute oropharyngeal palsy also was reported to have these antibodies [5]. We treated a patient with acute oropharyngeal palsy associated with an isolated anti-GM1 b IgG antibody. This autoantibody has yet to be reported in patients with regional GBS variants, although in more generalized cases it is regarded as a diagnostic marker of GBS [3]. A 47-year-old woman’s voice developed an increasingly nasal quality over a few days. She had no history of a preceding cough, fever, sore throat or diarrhea. Neurological examination on day 5 of her course showed mild dysarthria and mild weakness of neck flexion (Medical Research Council grade, 4). Palatal elevation was diminished and the gag reflex was absent. Pupil size and reactions were normal. No signs of ophthalmoplegia, ptosis, or facial muscle weakness were found. Limb muscle power and tendon reflexes were normal. The patient could not perform tandem gait, but finger-to-nose and heel-to-knee tests were normal. The Romberg test was negative. No sensory or autonomic disturbances were present. The complete blood count and blood chemistry results were normal. Results of serological tests for Campylobacter jejuni, cytomegalovirus, Mycoplasma pneumoniae, varicella-zoster virus, and herpes simplex virus infections were negative. On day 7, serum IgG antibody titer against GM1 b was found to be elevated (1:2,000; normal, less than 1:500). No IgG antibodies against GM2, GM1, GD1 a, GalNAc-GD1 a, GD1b, GT1 a, GT1 b, or GQ1 b were detected. IgM antiganglioside antibodies were absent. Cerebrospinal fluid obtained on day 7 showed normal protein and cell content. Motor nerve conduction studies on day 7 were normal. A sensory nerve action potential was not evoked in the sural nerve, but sensory nerve action potentials and sensory conduction velocities were normal in the median nerve. Cranial MRI with enhancement was normal. From day 10, the patient was given intravenous immunoglobulin (400 mg/kg/day) for 5 consecutive days. She noted some difficulty in swallowing on day 11, but did not require tube feeding. Dysphagia and dysarthria respectively disappeared by days 14 and 28, and all other neurologic abnormalities had resolved completely 2 months after onset. The anti-GM1 b IgG antibody titer had returned to the normal range (less than 500) 8 months following onset of illness. Our patient experienced acute progression of oropharyngeal palsy as well as mild truncal ataxia and neck weakness. She never showed notable limb weakness, ophthalmoplegia, ptosis, or areflexia. These clinical features are simitar to those of O’Leary’s patients with acute oropharyngeal palsy [4]. However, these patients had antiGQ1 b and anti-GT1 a IgG antibodies, while our patient had an antiGM1 b IgG antibody. Anti-GM1 b antibody is closely related to severe limb weakness and slow recovery in generalized GBS [7]. On the whole, GBS patients with anti-GM1 b antibodies are somewhat less likely to have cranial nerve involvement, although this antibody can be detected in half of GBS patients who show oropharyngeal palsy as an initial symptom [2, 6]. Several case reports suggest that anti-GT1 a IgG antibody, with or without cross-reactivity with GQ1 b, is involved in the pathogenesis of oropharyngeal palsy in GBS [1]. Our case supports an association of oropharyngeal palsy with antiGM1 b antibodies. GQ1 b ganglioside in human cranial nerves is believed to be a target of the humoral autoimmune response in patients with Fisher syndrome or GBS with ophthalmoplegia and anti-GT1 a IgG antibody coexists in these conditions. AntiGQ1 b and anti-GT1 a IgG antibodies have also appeared together in acute ophthalmoparesis, Bickerstaff ’s brain stem encephalitis, and the pharyngeal-cervical-brachial variant of GBS [2]. In addition to anti-GT1 a and anti-GQ1 b antibodies, we feel that anti-GM1 b IgG antibody may be a helpful diagnostic marker for acute oropharyngeal palsy in some patients. Since in GBS anti-GT1 a, anti-GQ1 b, and anti-GM1 b IgG antibodies frequently coexist, acute oropharyngeal palsy may represent an early clinical stage of GBS, pharyngeal-cervical-brachial variant of LETTER TO THE EDITORS

Rhombencephalosynapsis: clinical findings and neuroimaging in 9 children.

Rhombencephalosynapsis is a rare congenital abnormality characterised by dorsal fusion of the cerebellar hemispheres, agenesis or hypogenesis of the vermis, fusion of dentate nuclei and superior cerebellar peduncles. We describe 9 children, aged 1.5 to 6 years, with rhombencephalosynapsis. Isolated rhombencephalosynapsis was found in 2 patients, hydrocephalus in 3 children and another 3 children had ventriculomegaly. Additional supratentorial abnormalities were documented in 5 patients. Clinical findings ranged from mild truncal ataxia and normal cognitive abilities to severe cerebral palsy and mental retardation. No correlation between clinical findings and magnetic resonance imaging could be established so far.

Outcome in children with space-occupying posterior fossa arachnoid cysts.

While prognostic information for Dandy-Walker syndrome and non-progressive cerebellar ataxia/cerebellar hypoplasia is available, surprisingly scant literature reports are found for space-occupying posterior fossa arachnoid cysts (PFAC). We describe the outcome of patients with symptomatic PFAC shunted as infants. Only 11 children were seen over a 20-year period (1980-1999). Cyst location was retrocerebellar (n = 8), supravermian (n = 2) and in the cerebellopontine angle (n = 1). Motor and cognitive impairments in one child were interpreted as the result of neurosurgical complications (intraventricular and intracerebral haemorrhage). One 6-year-old boy had mild truncal ataxia and mild cognitive delay. The 9 other patients had no evidence of ataxia or clumsiness and had average, some even above average, cognitive ability and scholastic achievements. Epilepsy was not a feature. We conclude that the prognosis of PFAC for cognitive development and neurological signs is favourable.

Vitamin E deficiency during chronic childhood cholestasis: Presence of sural nerve lesion prior to 2½ years of age

Vitamin E malabsorption and deficiency during chronic childhood cholestasis has been associated with a progressive ataxic neurologic syndrome. Hyporeflexia, the first sign of neurologic dysfunction, may begin prior to age 2 years, but severe symptoms do not develop until age 5 to 10 years. To establish the age of onset of neuropathologic lesions, we prospectively evaluated four young children with severe cholestasis. Malabsorption and deficiency of vitamin E were documented by low serum vitamin E concentrations, low serum vitamin E to total serum lipids ratios, elevated hydrogen peroxide hemolysis, and impaired absorption of a pharmacologic dose of alpha-tocopherol. Abnormal neurologic findings in two patients were limited to areflexia, ptosis, mild truncal ataxia, and hypotonia; two patients had minimal signs of neurologic dysfunction. Sural nerve histology at age 6 to 25 months revealed a degenerative axonopathy involving large-caliber myelinated fibers, but without quantitative axonal loss. Muscle histology and histochemistry tests yielded normal results. Our study suggests that neurologic injury may occur during the first two years of life in vitamin E-deficient children with cholestatic hepatobiliary disease, obligating aggressive attempts at correcting this deficiency state at a very young age.