Toluene abuse causes diffuse central nervous system white matter changes

We describe the findings of magnetic resonance imaging (MRI) of the brain in 6 chronic toluene vapor abusers and the neuropathological findings in 1 abuser not studied by MRI. MRI in 6 chronic toluene abusers revealed the following abnormalities: (1) diffuse cerebral, cerebellar, and brainstem atrophy; (2) loss of differentiation between the gray and white matter throughout the central nervous system; and (3) increased periventricular white matter signal intensity on T2-weighted images. Another chronic toluene abuser (MRI not performed) died as a result of acute toluene overdose. The brain displayed diffuse, ill-defined myelin pallor, maximal in cerebellar, periventricular, and deep cerebral white matter. Neurons were preserved throughout, axonal swelling or beading was not seen, gliosis was minimal, and occasional, scant perivascular macrophage collections were seen. Taken in concert, these findings suggest that the pathological and MRI abnormalities are due to either increased water content of the white matter or subtle toluene-induced metabolic changes in myelin.     

Neurologic sequelae of chronic solvent vapor abuse

Neurologic abnormalities were seen in 13 of 20 patients with a history of chronic solvent vapor (primarily toluene) abuse for 2 or more years. The patients were evaluated after an abstinence period of at least 4 weeks, to avoid neurologic effects of acute intoxication. Neurologic signs included cognitive (60%), pyramidal (50%), cerebellar (45%), and brainstem/cranial nerve (25%) findings. Eight of nine CTs revealed diffuse atrophy of cerebral hemispheres, cerebellum, and brainstem. BAERs were abnormal in three of four patients, and EEG abnormalities were seen in three of seven patients. Chronic exposure to solvent vapor may cause persistent neurologic impairment.     

Multifocal central nervous system damage caused by toluene abuse

Four toluene abusers had evidence of severe multifocal central nervous system damage. Impairment of cognitive, cerebellar, brainstem, auditory, and pyramidal tract function, as well as CT evidence of cerebral cortical, cerebellar, and brainstem atrophy, have been noted. In addition, we found opsoclonus, ocular flutter, and ocular dysmetria. All three patients tested had abnormal brainstem auditory evoked potentials, indicative of brainstem dysfunction. The patient with opsoclonus had CT evidence of brainstem, cerebellar, and cerebral cortical atrophy.     

A case of chronic toluene intoxication with atrophy of cerebrum, cerebellum and brainstem on CT and MRI]

A 28-year-old man developed neurological disorders consisting of cerebellar symptoms and dementia over a period of 8 years of inhalation of toluene. He also developed bilateral optic atrophy. CT scan and MRI revealed atrophy of cerebrum, cerebellum and brainstem. The severity of neurological symptoms corresponded with the findings of CT and MRI. Furthermore, MRI (T2) showed reduced signal intensity in bilateral thalamus. This patient was also admitted to another hospital 2.5 years ago. Compared with the previous findings, present examinations showed significant progress of the atrophy of cerebrum and brainstem. It was suggested from the results of ABR that the disturbance of the brainstem was aggravated through this period.     

Clinical and magnetic resonance imaging features of elderly onset dentatorubral–pallidoluysian atrophy

Dentatorubral–pallidoluysian atrophy (DRPLA) is an autosomal dominant spinocerebellar ataxia caused by CAG triplet expansion in atrophin 1 and is frequently associated with cerebral white matter lesions. To elucidate the clinical features of elderly onset DRPLA and the key radiological findings for differentiating DRPLA from physiological white matter lesions in healthy elderly subjects, we reviewed the clinical and magnetic resonance imaging (MRI) features of ten patients with elderly onset genetically confirmed DRPLA (> 60 years) and compared their MRI findings with those of age- and sex-matched ten healthy subjects with asymptomatic cerebral white matter lesions. The initial symptom was cerebellar ataxia in all DRPLA patients, and five of them did not have any symptoms other than ataxia at the time of MRI examination. Atrophy of the brainstem, superior cerebellar peduncle, and cerebellum was detected in all DRPLA patients and none of the healthy subjects. Abnormal signals in the brainstem (inferior olive, pons, and midbrain), thalamus, and cerebellar white matter were frequently observed in elderly onset DRPLA patients but not in healthy subjects. In conclusion, elderly onset DRPLA presents as cerebellar ataxia alone in the early stage of disease. Atrophy of the brainstem, superior cerebellar peduncle, and cerebellum and abnormal signals in the brainstem, cerebellum, and thalamus are key findings for differentiating elderly onset DRPLA from asymptomatic cerebral white matter lesions in healthy subjects.     

Magnetic resonance imaging and clinical findings examined in adulthood-studies on three adults with Rett syndrome

Purpose: To clarify magnetic resonance imaging (MRI) findings in three adult patients with Rett syndrome who had been diagnosed with mental retardation and autism.Method: Clinical and MRI findings in three adult cases with Rett syndrome were studied. Ages (in years) in three adult cases with Rett Syndrome were 46 in Case 1, 35 in Case 2 and 20 in Case 3. They were able to walk and their convulsions were well controlled.Results: MRI findings in all patients showed mild cerebral atrophy, especially in the frontal and temporal lobes and two of the cases also had mild cerebellar atrophy. One case also showed a narrowing of the brainstem and thinning of the corpus callosum.Conclusions: These results indicate that abnormalities in MRI imaging, in cases where there is narrowing of the brainstem and thinning of the corpus callosum, may be due to congenital hypoplasia. It was also seen that cerebellar atrophy became more distinct in older cases.     

A case of late adult-onset dentatorubral-pallidoluysian atrophy mimicking central pontine myelinolysis

We report the case of a 52-year-old man with late-onset dentatorubral-pallidoluysian atrophy (DRPLA). MRI findings of late-onset DRPLA usually showed the involvement of cerebral white matter lesions with high intensity on T2-weighted images (WI), in addition to brainstem, globus pallidus, and thalamus. But our patient did not present with abnormal manifestation of white matter lesions of the cerebrum. In addition, the appearance of pontine base was remarkably similar to central pontine myelinolysis (CPM). There is no reported case of DRPLA mimicking CPM in the literature, while there is one previous report of CPM with cerebellar ataxia without pyramidal tract involvement, and CPM may exhibit cerebellar ataxia. Although there is differentiation between CPM and DRPLA by the presence of the atrophy of brainstem and cerebellum, the characteristic MRI findings of pontine base may make it difficult to differentiate CPM with cerebellar ataxia from DRPLA with inconspicuous leukoencephalopathy. In such a situation, we should return to the clinical history and background of a patient, and, if necessary, DNA analysis should be performed for a definite diagnosis.     

Multiple acute infarcts in the posterior circulation.

OBJECTIVE--to evaluate clinical, radiological, and prognostic features of patients with multiple acute infarcts in remote arterial territories of the posterior circulation. DESIGN--Data analysis from a prospective acute stroke registry in a community based primary care centre using a standard protocol including MRI and MRA. RESULTS--In three and a half years, 27 of the 236 patients (11%) with posterior circulation stroke had multiple acute infarcts in the posterior circulation as shown by gadolinium enhancement on MRI. Eighteen patients had multiple infratentorial and supratentorial infarcts including the cerebellum and posterior cerebral artery territory, with coexisting brainstem involvement in seven patients. Fourteen patients had a rostral basilar artery syndrome and cerebellar signs; four patients had a visual field defect with cerebellar signs. Causes were vertebral (six) or basilar (four) artery atheromatosis, and cardioembolism (four). Seven patients had multiple acute infarcts in the posterior circulation of the cerebellum and lower brainstem. Brainstem and cerebellar signs were found in most patients (five); aetiologies were small vessel disease (four), cardioembolism (one), and vertebral artery dissection (one). Two patients with large artery atheromatosis had multiple acute infarcts in the posterior circulation in the brainstem and posterior cerebral artery territory. One month after stroke more than 25% of the patients were dependent or had died. There was no difference in the outcome between the three groups, and recovery was linked to the size of infarcts rather than to a high number of infarcts. CONCLUSIONS--multiple acute infarcts in the posterior circulation usually involve the cerebellum. Simultaneous brainstem and posterior cerebral artery territory infarcts sparing the cerebellum are uncommon. They can be suspected clinically before neuroimaging, mainly when supratentorial and infratentorial infarcts coexist. This may be important, because different patterns of infarction are associated with different causes of stroke.     

Course of apparent diffusion coefficient values in cerebral edema of dural arteriovenous fistula before and after treatment

Apparent diffusion coefficient (ADC) values at magnetic resonance imaging (MRI) are useful to distinguish vasogenic and cytotoxic edema due to cerebovascular diseases. Dural arteriovenous fistulas (DAVFs) with retrograde leptomeningeal venous drainage may cause cerebral edema by venous congestion. We report herein the course of ADC values of cerebral edema before and after endovascular treatment in DAVFs. A 65-year-old woman with transverse-sigmoid (T-S) sinus DAVFs with retrograde leptomeningeal venous drainage presented with severe edema in cerebellar hemisphere and brainstem. In preoperative MRI, increased ADC values were observed in the edema area. The isolated sinus was obliterated completely by transvenous embolization. On the following day after treatment, the ADC values in cerebral edema area increased slightly without any new neurological deficits and improved at 1 week later. Rapid resolution of venous congestion due to DAVFs may cause a slight, transient progression of vasogenic edema.     

Relationship between abnormal respiratory control and perinatal brainstem and cerebellar infarctions

Clinical and neuropathologic studies were performed in 5 infants who had brainstem or cerebellar infarction and respiratory control abnormalities during early infancy. The anatomic distribution of brainstem infarction was closely related to the failure of neural respiratory control as was unilateral cerebral hemorrhagic infarction to sudden death. Brainstem and cerebellar lesions may be important in the pathogenetic mechanism of sleep apnea and sudden infant death syndrome due to brainstem tegmental gliosis and cerebellar respiratory control disturbance.     

Asymptomatic CTG expansion at the SCA8 locus is associated with cerebellar atrophy on MRI

Spinocerebellar ataxia type 8 (SCA8) is the first example of dominantly inherited ataxia reported to be caused by a dynamic mutation of the untranslated CTG trinucleotide repeat. We performed genetic and clinical analyses of a family with an isolated case with young onset cerebellar ataxia carrying an expanded 95 CTA/CTG repeats, and revealed that the asymptomatic father was also carrying a much greater expansion of 136 repeats. This paternal transmission developed a large contraction of -41 CTG repeats. The ataxia patient showed almost pure cerebellar symptoms, and a cerebral MRI of the patient demonstrated significant atrophy of the cerebellar vermis and hemispheres with preservation of brainstem and cerebrum. Although the father did not show any neurological abnormalities, his MRI demonstrated mild atrophy of the cerebellar hemispheres. The genetic phenomenon on this family has not been observed in other types of SCAs, and this reduced penetrance may cause reproduction of sporadic SCA8 frequently. Therefore, we must perform careful interviews regarding family history, and suggest the genetic and neuroradiological investigations on family members when we encounter a sporadic patient with the CTG expansion at the SCA8 locus.     

Diffuse cerebral hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum

Three unrelated Japanese patients who presented with ataxia and mild mental retardation were examined in this study. Early development was normal in two patients and slightly delayed in one. All could walk independently, but were unstable due to cerebellar ataxia. They had mild intellectual retardation and displayed slow, progressive, and mild clinical courses. Two patients lost the ability to walk at 12 and 25 years of age. Brain MRI of the three patients revealed diffuse cerebral hypomyelination, moderate cerebellar cortical atrophy, and hypoplasia of the corpus callosum, which were seen in other diffuse hypomyelination syndrome. No known abnormalities were found in biochemical and genetic studies. Auditory brainstem responses and nerve conduction studies were normal. A definite diagnosis could not be made because of the lack of hypodontia, hypogonadism, cataracts, or basal ganglia atrophy. Based on common MRI findings and the relatively mild clinical courses, we believe that these patients may have another subset form of diffuse hypomyelination syndrome involving the cerebral white matter and cerebellum.     

Cerebellar speech representation: lesion topography in dysarthria as derived from cerebellar ischemia and functional magnetic resonance imaging

BACKGROUND: Lesion topography and the pathophysiological background of dysarthria due to focal cerebellar lesions have not yet been fully clarified. OBJECTIVES: To investigate the lesion topography of dysarthria due to cerebellar ischemia and evaluate brainstem functions. DESIGN: Case studies. PATIENTS: Eighteen right-handed patients with sudden-onset dysarthria and cerebellar ischemia with and without brainstem involvement and 19 healthy, right-handed, monolingual, German-speaking volunteers. METHODS: In patients, we used multimodal electrophysiologic techniques to investigate brainstem functions. Functional magnetic resonance imaging (MRI) was performed in the 19 healthy volunteers. Activation tasks consisted of repetitive vertical silent movements of the tongue and lips at a self-paced rhythm. RESULTS: Cerebellar lesions and additional signs of brainstem involvement were observed in 11 patients with posterior inferior cerebellar artery, anterior inferior cerebellar artery, and superior cerebellar artery infarctions, respectively. In all other patients with isolated cerebellar infarction (n = 7), only the superior cerebellar artery territory (6 right-sided, 1 left-sided) was affected, and the common lesion site was the rostral paravermal region of the anterior lobe. Functional MRI in healthy volunteers indicated that the cerebellar representation of the tongue and orofacial muscles corresponds to that of the area involved in patients with cerebellar dysarthria. CONCLUSIONS: The results of this study demonstrate that articulatory movements of the tongue and orofacial muscles are involved in the activation of the rostral paravermal area of the anterior lobe. This location corresponds to the area involved in cerebellar ischemia in patients with dysarthria. Lesions in the upper paravermal area of the right cerebellar hemisphere, the site of coordination of articulatory movements of the tongue and orofacial muscles, may lead to the development of dysarthria that is unrelated to (often concomitant) brainstem infarctions.     

Magnetic resonance imaging in degenerative ataxic disorders.

MRI of the brain was performed in 53 patients with a variety of degenerative ataxias and related disorders and 96 control subjects. Atrophy of intracranial structures was not seen in patients with the pure type of hereditary spastic paraplegia, or in early cases of Friedreich's ataxia. In advanced Friedreich's ataxia there was atrophy of the vermis and medulla. The MRI features of early onset cerebellar ataxia with retained reflexes were variable, and suggest heterogeneity. In autosomal dominant cerebellar ataxias, most patients had cerebellar and brainstem atrophy, probably reflecting the pathological process of olivopontocerebellar atrophy; there was no clearly defined group with both clinical and imaging features of isolated cerebellar involvement. The MRI abnormalities in idiopathic late onset cerebellar ataxia were predominantly those of cerebellar and brainstem atrophy or pure cerebellar atrophy. The clinical and imaging features of brainstem abnormalities were discordant in several patients. Pure cerebellar atrophy was associated with slower progression of disability. Cerebral atrophy was common in the late onset ataxias. Cerebral white matter lesions, although usually few in number, were observed in significantly more patients than controls, particularly those aged over 50 years.     

A case of the subacute brainstem encephalitis

A case of brainstem encephalitis of undetermined etiology is reported in 66-year-old woman who had a sudden onset of illness with left abducens palsy, nystagmus and ataxia. The symptoms progressed to complete paralysis of eye movements, dysphagia and left hemiparesis with generalized hyperreflexia. Examination of CSF, CT scan and MRI of the brain were normal. The patient died 4 months after onset of disease. Neuropathologic study disclosed in the brainstem numerous perivascular and nodular inflammatory cell infiltrations composed predominantly of lymphocytes T and B. Most intensive inflammation concerned midbrain and pontine tegmentum and to a lesser degree medulla oblongata, pontine nuclei and cerebellar nuclei. Basal ganglia, cerebral and cerebellar cortex were unaffected. Neuropathological finding was reminiscent of brainstem encephalitides related to viral infection or to paraneoplastic syndrome. However, HSV-1, EBV, and CMV antigens were not detected by immunohistochemistry, as well as evidences of malignancy were not present in this case.     

The impact of magnetic resonance imaging on the management of acute ischemic stroke.

Despite rapid advances in imaging technology, the etiology of stroke remains unestablished in 40% of patients. MRI improves localization in acute stroke. However, it is not known whether "accurate localization" results in better management. We reviewed the hospital records of all patients admitted with a diagnosis of acute ischemic stroke and who had had cranial CTs and MRI within 10 days of admission. Between January 1987 and June 1990, 116 patients (69 men, 47 women; mean age, 66 years) were identified. Compared with CT localization, infarcts were better localized in nine of 39 patients with cerebral cortical lesions, in 20 of 22 patients with brainstem and cerebellar lesions, and in three of three patients with isolated cerebellar lesions. In 22 patients (18.9%), MRI showed multiple infarcts in two or more vascular territories, suggesting embolic disease and leading to anticoagulation. MRI also showed arterial occlusions in 11 patients (9.5%). Based on the information obtained with MRI, the clinical diagnosis was changed in 19 patients (16.3%), resulting in changes in the management of most of those patients. Thus, we confirm earlier reports that MRI improves localization after acute cerebral infarction and show that such information alters patient management.     

Ex vivo high-resolution magnetic resonance imaging of the brain in Joubert's syndrome

This study employs ex vivo high-resolution magnetic resonance imaging (MRI) to examine anatomic structures in an intact brain of a child with Joubert's syndrome. Several of the specific hindbrain malformations associated with Joubert's syndrome are well resolved with ex vivo MRI, including the "molar tooth sign," which arises from enlarged and maloriented superior cerebellar peduncles, hypoplastic vermis, and deepening of the interpeduncular fossa. Superior resolution was achieved compared with that of in vivo MRI and included visualization of the inferior olives. One high-resolution study also showed that the decreased width of the brainstem isthmus is probably caused by failure of superior cerebellar peduncles to cross the midline at that level. The results of this study suggest that high-resolution MRI may be useful in screening the brainstem for malformations that can be studied histologically in a much more targeted fashion.     

Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case with distinct MRI findings

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a recently described disorder with autosomal recessive mode of inheritance. Lately, mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase, have been found as the underlying defect. We report a 19-year-old male patient with cerebellar, pyramidal and dorsal column dysfunctions and specific magnetic resonance imaging (MRI) and characteristic magnetic resonance spectroscopy (MRS) abnormalities. The patient was compound-heterozygous for two mutations in DARS2. MRI showed selective involvement of cerebral and cerebellar white matter and superior and inferior cerebellar peduncles, without contrast enhancement. The U-fibers were spared. The sensory and the pyramidal tracts were affected over their entire length. Involvement of the intraparenchymal trajectories of the trigeminal nerves and mesencephalic trigeminal tracts was demonstrated. In the spinal cord, signal abnormalities were identified in the dorsal columns and the lateral corticospinal tracts. Proton-MRS of the frontal and cerebellar white matter showed elevated lactate, reduced N-acetylaspartate, increased myoinositol and mildly elevated choline. In LBSL, distinct MRI findings should lead to the diagnosis, which can be confirmed by the analysis of the disease gene DARS2.     

X-linked adrenoleukodystrophy with olivopontocerebellar atrophy.

X-linked adrenoleukodystrophy (X-ALD) is a rare neurological disorder characterized by adrenal, gonadal and nervous system dysfunction. Patients usually develop spinal cord degeneration with involvement of the cerebral white matter. While a spinocerebellar variant has been described, the selective involvement of cerebellar white matter is very rare. We report the case of a patient affected by X-ALD whose clinical and magnetic resonance imaging (MRI) results resembled olivopontocerebellar atrophy. He was a 29-year-old mentally retarded man, who began to complain of slowly progressive gait ataxia after an 8-year history of Addison's disease. Serial MRI revealed marked cerebellar atrophy involving the inferior cerebellar vermis and brainstem, but sparing the supratentorial white matter. The diagnosis of X-ALD was confirmed by elevated levels of very long-chain fatty acids in the serum. After 2 years follow-up, the patient developed spastic paraparesis. The patient represents an unusual clinical presentation of X-ALD, as further confirmed by the MRI results. Consequently, cerebellar symptoms should be considered as a clinical presentation of X-ALD. Early recognition of this rare disorder would be useful for genetic counselling and therapy.