Type 2 atrophy in a pentazocine addicted patient

A case of a 33-year-old pentazocine-addicted man (450 mg daily) is described. Histochemical and quantitative histographic analyses of the muscle biopsy disclosed type 2 atrophy.We consider that this indicates that there is a generalized toxic effect of pentazocine.     

Camptocormia in a patient with multiple system atrophy.

The term "camptocormia" describes a severe forward-flexed posture. Although initially used to describe a conversion disorder, early authors also recognized organic camptocormia occurring in old age, or "camptocormie senile," as well as traumatic and arthritic camptocormia. More recently, camptocormia has been described in patients with Parkinson's disease and in an individual with parkinsonism. We describe a case of progressive camptocormia as part of the initial presentation of a patient with multiple system atrophy.     

Successful botulinum toxin treatment of dysphagia in a spinal muscular atrophy type 2 patient

Prominent dysphagia is seen among patients with spinal muscular atrophy (SMA) type 2, especially at the late stage of their disease progression. Nasogastric tube feeding and gastrostomy are commonly utilized to maintain their nutritional status. However, choosing a treatment strategy to maintain appropriate nutritional status is often complicated by multiple factors, such as physical conditions and social aspects. We report a 21-year-old man with SMA type 2 who has been suffering from severe dysphagia. The findings at video-fluoroscopic swallow study (VSS) were consistent with a diagnosis of cricopharyngeal dysphagia. His dysphagia was successfully treated with percutaneous injection of botulinum toxin A (BTA) into the cricopharyngeal muscle. Our result demonstrates that administration of BTA is one of the effective treatment choices for dysphagia in SMA patients.     

Cortical atrophy in the cerebellar variant of multiple system atrophy: a voxel-based morphometry study.

This study aimed to determine in vivo the atrophy patterns in clinically established cerebellar variant of multiple-system atrophy (MSA-C) using voxel-based morphometry (VBM). Thirteen patients with MSA-C (12 probable, 1 possible) and 13 healthy controls matched for age and sex were included. High-resolution MR images were acquired with a 1.5 T scanner. Images were normalized onto a study-specific template, segmented into the tissue compartments, modulated with the Jacobian determinants, and finally smoothed with a Gaussian kernel filter of 10 mm. The general linear model was used to assess statistical differences in gray and white matter. Infratentorial atrophy was observed in the cerebellar hemispheres, vermis, mesencephalon, and pons of MSA-C patients. Supratentorial volume loss was found in orbitofrontal and mid-frontal regions as well as in temporomesial and insular areas of both hemispheres. A negative correlation was observed between a cerebellar ataxia score and the volume of cerebellar hemispheres, peduncles, and pons. To compare this atrophy pattern to that of spinocerebellar ataxia (SCA2), which was previously reported by our group, a conjunction analysis was assessed. We observed a volume loss shared by both disorders comprising the cerebellum, vermis, pons, mesencephalon, orbitofrontal, mid-frontal, and temporomesial cortex of both hemispheres as well as the left insular cortex.     

Multiple system atrophy in a patient with the spinocerebellar ataxia 3 gene mutation.

The cerebellar variant of multiple system atrophy (MSA-C) has overlapping clinical features with the hereditary spinocerebellar ataxias (SCAs), but can usually be distinguished on a clinical basis. We describe a patient who developed a sporadic, late-onset, rapidly progressive neurodegenerative disorder consistent with MSA-C. Genetic testing, however, showed an abnormal expansion of one allele of the spinocerebellar ataxia 3 (SCA3) gene. The clinical impression of MSA-C was confirmed by identification of numerous alpha-synuclein-containing glial cytoplasmic inclusions on autopsy. These findings suggest that abnormal expansion of the SCA3 gene may be a risk factor for the development of MSA-C.     

Hypertrophic type of peroneal muscular atrophy and spinal muscular atrophy in siblings

We describe a family with one brother suffering from a hypertrophic type of peroneal muscular atrophy, and a sister suffering from a late infantile from of spinal muscular atrophy. There are no other affected members in the relatives studied. This association has not been previously described, and has appeared as a result of a consanguineous marriage.     

Progressive cerebral atrophy in multiple system atrophy

Nine patients with multiple system atrophy (MSA) were studied based on MRI findings of cerebral hemispheric involvement. The age at onset was 56.4+/-8.6 (mean+/-S.D.) years, duration of illness at the first MRI study 2.1+/-1.1 years, duration of illness at the last study 9.7+/-2.6 years, and the follow-up duration 7.6+/-2.3 years. Controls were 85 neurologically intact persons (60.2+/-11.1 years age). In the MRI study, measurements of the ratio of each area to the intracranial area were performed for the cerebral hemisphere, frontal, temporal and parietal-occipital lobes. A significant progression of atrophy to under the normal limit was observed in the cerebrum, frontal and temporal lobes. Besides the typical pathological lesions in MSA, five autopsied patients revealed frontal lobe atrophy with mild gliosis, mild demyelination and glial cytoplasmic inclusions (GCIs). One of these patients showed remarkable frontal lobe atrophy with degenerative changes in the cerebral cortex. We observed the involvement of the cerebral hemisphere, especially the frontal lobe.     

Life-threatening respiratory failure due to cranial dystonia after dental procedure in a patient with multiple system atrophy.

We report on a woman with a an 8-year history of multiple system atrophy with predominance of parkinsonism who developed jaw-locking oromandibular dystonia within hours after insertion of ill-fitting dentures. Dystonia spread rapidly to involve other facial muscles and the larynx causing stridor with respiratory failure necessitating crush intubation.     

G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with multiple system atrophy.

Multiple system atrophy (MSA) is characterized clinically by Parkinsonism, cerebellar dysfunction, and autonomic impairment. Multiple mutations in the LRRK2 gene are associated with parkinsonian disorders, and the most common one, the G2019S mutation, has been found in approximately 1% of sporadic cases of Parkinsonism. In a well-characterized cohort of 136 subjects with probable MSA and 110 neurologically evaluated control subjects, none carried the G2019S mutation. We conclude that the G2019S mutation in the LRRK2 gene is unlikely to be associated with MSA.     

SMA区域存在大片段缺失的脊髓型肌萎缩症3型患者：1例报告

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration and loss of anterior horn cells in the spinal cord and brain stem nuclei,leading to progressive limb and trunk paralysis and muscular atrophy.Depending on the age of onset and maximum muscular function achieved,SMA is recognized as SMA1,SMA2,SMA3 or SMA4,and most patients have a deletion or truncation of the survival motor neuron 1 (SMN1) gene.In this report,we present a patient with a mild SMA phenotype,SMA3,and define his genetic abnormality.Tetra-primer amplification refractory mutation system PCR combined with restriction fragment length polymorphism analysis and array comparative genomic hybridization were used to determine the genetic variations in this patient.A 500 kb deletion in chromosome 5q13.2,including homozygous deletion of neuronal apoptosis inhibitory protein,and heterozygous deletion of occludin and B-double prime 1 was identified.This SMA region deletion did not involve SMN,indicating that SMN was likely to function normally.The phenotype was dependent of the large deletion and neuronal apoptosis inhibitory protein,occludin and B-double prime 1 may be candidate genes for SMA3.     

Neuronal loss in the basal nucleus of Meynert in a patient with olivopontocerebellar atrophy

Summary A morphometric study of the basal nucleus of Meynert has been performed in a case of familial olivopontocerebellar atrophy with mental deterioration. The magnocellular population of the basal nucleus found to be substantially reduced in number (over 60%) as compared with that of three agematched controls. This finding has not been reported previously and might represent one of the antomic substrates of some of the cognitive disturbances exhibited by a considerable number of patients with olivopontocerebellar atrophy (OPCA).     

A patient with simplified gyral pattern followed by progressive brain atrophy

We present the case of a three-year-old boy who suffered from intractable epilepsy from birth, and who displayed microcephaly and severe developmental delay. Neuroradiological examination revealed the presence of simplified gyri of the cerebral cortex, and increased signal intensity changes in the cerebral white matter on T2-weighted magnetic resonance imaging. A tentative diagnosis of congenital cortical malformation was made, but unexpectedly, the cerebrum, cerebellum, and pons showed a progressive atrophy during the follow-up period. The basal ganglia and thalamus were relatively spared. Investigations could find no evidence of leukodystrophies, metabolic disorders, hereditary brain anomalies, or congenital central nervous infections. This case may represent a novel type of neurodegenerative disease with malformation of cortical development.     

Type II neurofibromatosis presenting as quadriceps atrophy

A young woman aged 26 years presented with atrophy of the left quadriceps progressing over one year. Magnetic resonance imaging (MRI) showed a large lesion of the lumbar plexus compatible with neurinoma. Cerebral MRI revealed a lesion in the right eighth cranial nerve also compatible with neurinoma. On further questioning of the patient, it was learned that her mother had undergone surgery twice for acoustic neurinoma. Type II neurofibromatosis was diagnosed from the basis of clinical picture, neuroimaging findings and family history. This case is unusual for the lack of central nervous system (CNS) symptoms. Expansive radicular lesions compatible with neurinoma should prompt cerebral MRI. Regular examination of family members at risk and early diagnosis can decrease the high mortality associated with this condition.     

Olivopontocerebellar atrophy: toward a better nosological definition.

Olivopontocerebellar atrophy (OPCA) is a pathological label implying not only olivopontocerebellar changes, but also cases with more widespread lesions involving the CNS. This polytopic pathological background accounts for clinical complexity, essentially defined as cerebellar-plus syndrome. The term "OPCA" is applicable to an increasing number of neurodegenerative syndromes, including autosomal dominant ataxia, complicated spastic paraplegia, multiple-system atrophy (MSA), and many cases of idiopathic late-onset cerebellar ataxia (ILOCA), some of whom also turn out to have MSA. OPCA may also be part of the pathological hallmark of other disorders, such as prion disorders, mitochondrial encephalomyopathies, and hereditary metabolic diseases. Sporadic OPCA and ILOCA with cerebellar-plus presentation and neuroimaging evidence of brainstem and cerebellar atrophy may represent interchangeable eponyms. Just a quarter of such cases evolve to MSA within 5 years of the onset of symptoms. Therefore, the assumption that MSA and sporadic OPCA necessarily are one and the same disease is no longer tenable. Our review suggests that the label "OPCA" is useful to designate a clinicopathological syndrome that has a variety of etiologies carrying a poor prognosis, particularly if associated with autonomic failure as occurs in MSA.     

Supratentorial atrophy in spinocerebellar ataxia type 2: MRI study of 20 patients

There have been only few studies of brain magnetic resonance imaging (MRI) in spinocerebellar ataxia (SCA) type 2. We investigated 20 SCA2 patients, from 11 Sicilian families, and 20 age-matched control subjects using MRI. Our data confirm that olivopontocerebellar atrophy (OPCA) is the typical pattern in SCA2. We found no significant correlation between infratentorial atrophy, disease duration, or the number of CAG repeats in our SCA2 patients, but there was supratentorial atrophy in 12 patients, with a significant correlation between supratentorial atrophy and disease duration. OPCA appears to represent the “core” of the SCA2: however, central nervous system involvement is not limited to pontocerebellar structures. We therefore consider central nervous system degeneration in SCA2 as a widespread atrophy. MRI is helpful in diagnosing SCA, but it is not diagnostic in the absence of clinical and molecular studies. We suggest that serial MRI may play a role in evaluating “in vivo” the progressive steps of neurodegeneration in SCA2, for a better comprehension of the pathophysiology of this disorder. Received: 22 June 1998 Received in revised form: 29 September 1998 Accepted: 13 October 1998     

Unusual findings on PET study of a patient with posterior cortical atrophy

We present a patient with posterior cortical atrophy in whom positron emission tomography (PET) showed unusual findings. This 65-year-old man had a 5-year history of slowly progressive apperceptive visual agnosia and Balint syndrome, but with a relatively well-preserved intelligence and language ability even in the later stages of illness. No relevant features in this patient or his family were identified. Laboratory and radiographic investigations indicated that cerebral damage was due to primary degeneration. His symptoms resembled those of patients with posterior cortical atrophy. A PET study revealed that cerebral metabolism was reduced in the dorsal regions of the entire cortex and asymmetrical with the main site of damage on the right. The severity in asymmetry increased dorsally. These 2 types of predilection for dorsal regions had not previously been reported in such patients. These unusual PET findings may indicate the presence of pathological changes not yet identified.     

White matter T2 hyperintensity development and clinical deterioration after status epilepticus in a patient with dentatorubral-pallidoluysian atrophy

Serial T2-weighted magnetic resonance imaging in a 29-year-old woman with juvenile type dentatorubral-pallidoluysian atrophy (DRPLA) demonstrated that a cerebral white matter hyperintensity appeared within 2 months after status epilepticus and persisted for more than 20 months. The patient had rapidly progressive mental regression and became akinetic after status epilepticus. The chronological relationship between the signal changes and the clinical deterioration suggested that the epilepsy, at least in part, contributed to the progression of white matter degeneration, the hallmark of DRPLA.     

LRRK2 and parkin immunoreactivity in multiple system atrophy inclusions

Certain genetic defects in LRRK2 and parkin are pathogenic for Parkinson’s disease (PD) and both proteins deposit in the characteristic Lewy bodies. LRRK2 is thought to be involved in the early initiation of Lewy bodies. The involvement of LRRK2 and parkin in the similar cellular deposition of fibrillar α-synuclein in glial cytoplasmic inclusions (GCI) in multiple system atrophy (MSA) has not yet been assessed. To determine whether LRRK2 and parkin may be similarly associated with the abnormal deposition of α-synuclein in MSA GCI, paraffin-embedded sections from the basal ganglia of 12 patients with MSA, 4 with PD and 4 controls were immunostained for LRRK2, parkin, α-synuclein and oligodendroglial proteins using triple labelling procedures. The severity of neuronal loss was graded and the proportion of abnormally enlarged oligodendroglia containing different combinations of proteins assessed in 80–100 cells per case. Parkin immunoreactivity was observed in only a small proportion of GCI. In contrast, LRRK2 was found in most of the enlarged oligodendroglia in MSA and colocalised with the majority of α-synuclein-immunopositive GCI. Degrading myelin sheaths containing LRRK2-immunoreactivity were also observed, showing an association with one of the earliest oligodendroglial abnormalities observed in MSA. The proportion of LRRK2-immunopositive GCI was negatively associated with an increase in neuronal loss and α-synuclein-immunopositive dystrophic axons. Our results indicate that an increase in LRRK2 expression occurs early in association with myelin degradation and GCI formation, and that a reduction in LRRK2 expression in oligodendroglia is associated with increased neuronal loss in MSA.     

Survival in multiple system atrophy: a study of prognostic factors in 59 cases

The various clinical features of multiple system atrophy (MSA) make the diagnosis of the disease difficult, especially in its early stages, when signs of differentiated neuroanatomical system involvement have not yet appeared. Mortality studies may be affected by the variability of the diagnostic criteria and selection bias. We used strict clinical and MRI criteria to diagnose MSA in 59 patients. Patients with parkinsonian and cerebellar onset were compared. Median survival time from the onset of the first motor symptom was 7.5 years. Our results indicated a trend (P = 0.09) for the Northwestern University Disability Scale score to correlate with mortality, but we failed to find other characteristics identifying subgroups or predictors for survival.