MRI volumetry of the vermis and the cerebellar hemispheres in men with schizophrenia

An association between cerebellar abnormalities and different manifestations of schizophrenia is increasingly hypothesized, either at the motor (anterior vermis), affective/psychotic (posterior vermis), or cognitive (cerebellar hemispheres) level. However, morphometric and volumetric cerebellar measurements have yielded highly divergent results. The main goal of this study was to use magnetic resonance imaging (MRI) to separately estimate the volumes of the entire vermis, the cerebellar hemispheres and three midsaggital vermian areas among 38 men with schizophrenia and 26 healthy men. Compared with the control group, persons with schizophrenia had significantly smaller volumes of the whole vermis, but not of the cerebellar hemispheres, a difference that approached significance when only the patients without a comorbid diagnosis of alcohol abuse/dependence were considered. Significant anomalies of the posterior vermian areas (lobules VI and VII) were detected in both subgroups of patients, while abnormalities of the anterior vermis (lobules I-V) were observed only among patients with a dual diagnosis of alcoholism. No difference emerged between the groups at the inferior vermian level (lobules VIII-X). Overall, these findings corroborate the hypothesized association between schizophrenia and specific posterior vermian anomalies, which might not necessarily be the consequence of alcohol abuse. However, the suggestion that schizophrenia is related to abnormal volumes of the lateral cerebellum is not supported.     

A rare saccade velocity profile in Stiff-Person Syndrome with cerebellar degeneration

Stiff-Person Syndrome (SPS) is an immune-mediated disorder of the central nervous system characterized by muscle rigidity, episodic muscle spasms, and high titers of antibodies against glutamic acid decarboxylase (GAD). The presence of cerebellar ataxia in SPS is extremely rare, but occurs. Clinical observations of ocular motor abnormalities have been noted in a few SPS patients. The purpose of this study is to provide a detailed quantitative documentation of ocular motor abnormalities in a patient with SPS and progressive cerebellar signs. Detailed clinical assessment of a woman with SPS and precise eye movement recordings using the magnetic search coil technique was performed. In addition to other ocular motor abnormalities that included longer latencies for saccades, downbeat nystagmus, and loss of downward smooth pursuit, a rare saccade velocity profile consisting of multi-component saccades was observed. We postulate that these ocular motor findings are related to impairment of GABAergic neurotransmission because antibodies to glutamic acid decarboxylase (GAD-Abs) have been implicated in the pathogenesis of both SPS and some cases of cerebellar ataxia. In addition, this unusual saccadic velocity profile may have important implications for modeling the saccadic system and furthering a complete understanding of saccade generation.     

Neuronal ceroid lipofuscinosis type-11 in an adolescent

Neuronal ceroid lipofuscinosis (NCL) is a group of progressive neurodegenerative disorders characterized by intracellular accumulation of ceroid lipopigments. Based on gene defect of NCL-associated proteins, 14 types of NCL have been described till date. NCL type 11 was first described in 2014 in two siblings as adult-onset NCL and was found to be due to a homozygous progranulin gene mutation. These siblings had progressive retinopathy, recurrent generalized seizures, moderate ataxia and subtle cognitive dysfunction. Palinopsia was present and MRI showed selective and severe cerebellar atrophy which was progressive with age. There have been no further reports of NCL 11 in literature. We here present a 14-year old girl born to second degree consanguineous couple who presented with gradually increasing frequency of seizures for the past 1?year without any signs of visual abnormalities and dementia. She had an elder sister who had progressive seizures and dementia from 8?years of age and died after few years. Her electroencephalogram showed frequent generalized epileptiform discharges and magnetic resonance imaging (MRI) showed pure cerebellar atrophy mainly affecting the vermis. MRI findings suggested a neurodegenerative disorder like NCL and prompted us to go for whole exome screen which revealed NCL type 11 due to homozygous mutation c.912G>A (p.Trp304Ter) in exon 9 of GRN gene (OMIM#614706). To the best of our knowledge this is the third case of NCL 11 and the first from Asia.     

Speech, cognition, and imaging studies in congenital ocular motor apraxia

Detailed neurological, speech and language, psychological, and neuroimaging studies were carried out in eight children with the diagnosis of congenital ocular motor apraxia. The neurological examination showed clinical evidence of cerebellar vermis abnormality (hypotonia and truncal ataxia) in all cases. Neuroimaging studies suggested that the site of neuropathological disturbance of congenital ocular motor apraxia was the inferior vermis. Half of the subjects had associated speech apraxia. The most likely location of brain disturbance, which was responsible for the speech apraxia, was also an as yet undefined area of the vermis. Psychological testing consistently revealed visual-spatial difficulties. These may have been secondary to cerebellar pathology or to developmentally inappropriate sensory input caused by the abnormal saccades. Children with speech apraxia appear to be slightly more affected neurologically than those with normal speech.     

Congenital ocular motor apraxia: clinical and neuroradiological findings, and long-term intellectual prognosis

The severity of intellectual sequelae and prognosis varies in patients with congenital ocular motor apraxia (COMA). Here, we explored this phenomenon with regard to the accompanying oculomotor signs and gross motor development, as well as the subtentorial structure defects. Ten patients diagnosed with COMA (M:F=4:6, 4-37 years old) were reviewed. Four individuals who gained the ability to walk at 2 years or earlier showed normal intellect and social skills. Those who walked later often showed accompanying intellectual (5/6) and speech (6/6) disabilities. In this latter group, atypical oculomotor signs for COMA (presence of nystagmus, mild limitation of vertical gaze, slower head thrust, and marked improvement of lateral saccade during early childhood) were often noted (4/6). Minor anomalies of fingers and toes were also common in this group. Neuroimaging was conduced in nine patients (pneumoencepharography 1; computed tomography: 8, magnetic resonance imaging: 2). Dilatation of the fourth ventricle, mainly at the level of the midbrain or upper pons (n=7), and hypoplastic cerebellar vermis (n=6) were commonly observed in both the early- and late-walking groups. 'Molar tooth' signs (n=3) were exclusively noted in the late-walking group, and often accompanied by atypical oculomotor signs (3/3) and intellectual disabilities (2/3). Vermian hypoplasia and dilatation of the fourth ventricle at the upper brainstem level in COMA patients, with or without intellectual disabilities, suggested that the cardinal lesion for OMA may exist in these areas. The presence of a subset of 'atypical' COMA patients may suggest that COMA with subtle infratentorial abnormality represents a heterogeneous disease category, showing similar oculomotor disturbance. This review indicated that clinical and neuroradiological inspection might be valuable for prediction of long-term intellectual prognosis in COMA patients.     

Microcephaly associated with Legg-Calvè-Perthes disease in two siblings

The co-occurrence of microcephaly and Legg–Calvè–Perthes disease (LCPD) in members of the same family has been previously recorded only in two Hungarian brothers. To study the clinical and radiological phenotype in a (second) family with LCPD and microcephaly, clinical, X-ray and MRI follow-up study of two Albanian siblings aged 8 and 11?years, were made. Both siblings had primary microcephaly, seizures and mild-to-moderate mental retardation. At head imaging the boy was found to have skull asymmetry, partial lack of frontal lobe development and partial agenesis of corpus callosum and the girl had a complex brain malformation consisting in thickening of the fronto-temporal cortex, colpocephaly, increased curvature of the Sylvian fissure, elevated tentorium with mild hypoplasia of the cerebellar vermis and dilated cisterna magna. In addition, the brother had ADHD and the sister minor eye anomalies mainly consisting in epicanthic folds and pale bilateral (temporal) optic disk. We recorded (and documented for the first time by brain MRI) a second family with familial co-occurrence of LCPD and microcephaly and the first occurrence of complex brain anomalies in the context of a small head circumference. The present report could encourage the observation of similar cases.     

Paroxysmal cerebellar ataxia--an evaluation using the findings from magnetic resonance imaging, positron emission tomography, and acetazolamide treatment

Paroxysmal cerebellar ataxia (PCA) is a specific disease which exhibits spasmodic cerebellar ataxia but rarely shows abnormal neurological findings in the intermission. Verger first described an isolated case. Subsequent reports of the disease included mostly cases with autosomal dominant inheritance, but the reports have been limited to about 20 families. Although both the lesion and the cause have not been clearly identified, since Vighetto et al. demonstrated the atrophy of the anterosuperior region of the cerebellar vermis using magnetic resonance imaging (MRI), the lesion of PCA captured the attention of researchers. The patient was a 40-year-old male, who exhibited spasmodic inarticulation and dizziness during walking when he was 10 years old. The symptoms gradually became aggravated in both frequency and duration. Abnormal findings were observed by electroencephalography and Hydantol F was given with no successful effect. The results of a CT scan of the head revealed no abnormality, whereas those of MRI revealed the atrophy in the folia of anterosuperior region of the cerebellar vermis by MRI as in the case of Vighetto et al., and PCA was suspected. Findings from positron emission tomography (PET) for the first time disclosed the abnormality in the cerebellar vermis and brainstem, and suggested an organic disorder in the cerebellar vermis and a functional abnormality in the cerebellum and brainstem. Since the report by Griggs et al., it has been known that acetazolamide is effective for PCA although the pharmacological mechanism is not yet clear. In our present case, the attack was improved in both frequency and duration by the administration of acetazolamide, and the effectiveness of acetazolamide in the patient was confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Horizontal eye movement disorders after posterior vermis infarctions.

The horizontal saccade, smooth pursuit, and vestibulo-ocular reflex gains were recorded in 19 patients with cerebellar infarction documented with MRI, and in a group of control subjects. Bilateral saccade hypometria and a decrease in ipsilateral smooth pursuit gain were found only in patients with a lesion affecting the posterior vermis. These results in humans support experimental findings suggesting that the posterior vermis controls both saccade accuracy and smooth pursuit velocity.     

Leber's congenital amaurosis. Relationship of structural CNS anomalies to psychomotor retardation

Three patients (two of them siblings) had Leber's congenital amaurosis and cerebellar disease. Despite blindness and severe motor deficits, all three patients have achieved relatively normal intellectual and psychosocial milestones. Computed tomographic scans, performed in two patients, demonstrated hypoplasia of the cerebellar vermis in both. The presence of delayed speech and motor development as well as structural CNS abnormalities in children with Leber's congenital amaurosis does not necessarily imply that severe intellectual impairment will be present.     

An MRI study of hereditary spinocerebellar degenerations

We evaluated magnetic resonance image (MRI) in 21 cases of hereditary spinocerebellar degenerations (SCD) of autosomal dominant trait. By the discriminant formula based on size of the cerebellar vermis and ventral pons, which was reported in our previous study, the patients were classified into three types. Group 1 included the cases with atrophies in the vermis and pons; OPCA type. Group 2 showed vermian atrophy and less significant atrophy in pons; LCCA type. And Group 3 was no significant atrophies both in vermis and pons. Cases in Group 1 were furthermore divided into two groups according to width of the midbrain tegmentum. Group 1A, with normal midbrain tegmentum, was consisted of five cases. Four cases were diagnosed as Menzel type OPCA. Another case showed various clinical symptoms and relatively mild atrophies for his duration of illness. His family members were classified to Group 3. Seven cases in Group 1B showed reduced midbrain tegmentum. Four cases showed ataxia, spasticity, ocular symptoms, bladder dysfunction and amyotrophy with or without fasciculation, and they seemed to be a special type of SCD mimicking Joseph disease. One case showed bulging eyes, ocular movement palsy and dystonia. However, his sister manifested only ataxia with very mild ocular movement disorder. Their MRI demonstrated severe atrophies in the cerebellum, pons and afferent cerebellar peduncli, and this pedigree was thought to be Menzel type OPCA with various associated disorders. Another case was clinically diagnosed as dentate-rubro-pallido-luysian atrophy. Group 2 was consisted of 6 cases who were clinically diagnosed as Holmes type LCCA. MRI demonstrated medial dominant cerebellar atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activation of cerebellar hemispheres in spatial memorization of saccadic eye movements: an fMRI study

What mechanisms allow us to direct a precise saccade to a remembered target position in space? The cerebellum has been proposed to be involved not only in motor and oculomotor control, but also in perceptual and cognitive functions. We used functional MRI (Echoplanar imaging at 1.5 T) to investigate the role of the cerebellum in the control of externally triggered and internally generated saccadic eye movements of high and low memory impact, in six healthy volunteers. Memory‐guided saccades to remembered locations of 3 targets (triple‐step saccades) in contrast to either central fixation or to visually guided saccades activated the cerebellar hemispheres predominantly within lobuli VI‐crus I. The same areas were activated when an analogous visuospatial working memory task was contrasted to the triple‐step saccades. Visually guided saccades activated the posterior vermis and the triple‐step saccades, contrasted to the working memory task, activated predominantly the posterior vermis and paravermal regions. Our data confirm the primary involvement of the posterior vermis for visually‐triggered saccadic eye movements and present novel evidence for a role of the cerebellar hemispheres in the mnemonic and visuospatial control of memory‐guided saccades. Hum. Brain Mapp. 22:155–164, 2004. © 2004 Wiley‐Liss, Inc.     

Visually and memory guided saccades in a case of cerebellar saccadic dysmetria.

Saccades under four specific test conditions (visually guided, visually remembered, vestibular remembered, and cervical remembered) were studied in a 38 year old man with ocular dysmetria due to an angioma of the dorsal cerebellar vermis. The aim of the study was to investigate if the saccadic disorder was specific to certain subsets of saccades elicited by different sensory modalities. The experiments showed that initial saccades were equally hypermetric in all four conditions and that final eye position was normal in all memory guided saccade tests. Eye movements differed after the initial saccade, however. Whereas corrective saccades were seen in most visually guided and visually remembered experiments, postsaccadic centripetal drifts were documented in non-visual (vestibular and cervical) remembered saccades. These results indicate that the cerebellar vermis modulates the amplitude of the initial saccade (pulse size of saccadic innervation) independently of the saccadic task. The finding that post-saccadic drift never occurred when saccades were programmed using visual positional information suggests that the dorsal vermis may participate in the process of pulse step integration of saccades elicited by memorised vestibulo-cervical information.     

Cerebellar Activation Related to Saccadic Inaccuracies

Using functional MRI, we assessed activity in the human cerebellum related to the properties of post-saccadic visual errors that drive the plasticity of saccadic eye movements. In the scanner subjects executed blocks of saccadic eye movements toward a target that could be randomly displaced during the saccade. Such an intra-saccadic shift was randomly forward or backward, and could be either small or large. Post-saccadic visual errors induced activation in several cerebellar areas. These areas included, but were not limited to, the oculomotor vermis which is known for its role in saccadic control. Large errors yielded more activation in the cerebellar hemispheres, whereas small errors induced more activation in the vermis. Forward shifts induced more activation than backward shifts. Our results suggest that the differences in cerebellar activation patterns for different sizes and directions of post-saccadic errors could underlie the behavioral differences observed between various saccadic adaptation paradigms. In addition, the outcome argues for an extended range of cerebellar target areas in electrophysiological studies on saccadic eye movement control.     

Isolated ocular motor nerve palsy in dural carotid-cavernous sinus fistula

The incidence of dural carotid-cavernous sinus fistula (DCCF) presenting as isolated ocular motor nerve palsies without congestive ocular features is unknown. We reviewed the DCCF patients in our hospital during the last 10 years to elucidate the clinical and neuroradiological features of DCCF with isolated ocular motor nerve palsy. Eleven amongst the 33 DCCF patients presented isolated ocular motor nerve palsy. All the 11 patients underwent brain CT/CT angiography (CTA) and/or MRI/MR angiography (MRA), before the digital subtraction angiography (DSA). The compromised nerves were the oculomotor nerve in eight (72.7%), abducens nerve in two (18.2%) and trochlear nerve in one (9.1%). Brain CT and/or CTA were conducted in four patients but all unremarkable. MRI and/or MRA were performed in nine patients and six of them showed compatible findings of DCCF. The diagnoses of DCCFs were confirmed by DSA and all were posterior-draining type. The outcome was good, with a total recovery rate of 54.5% within 12 months. Thirty-three percent (11 of 33) of our DCCF patients presented with isolated ocular motor nerve palsy, which is not uncommon. MRI and MRA are of value in the initial evaluation, but DSA is necessary for the accurate diagnosis and treatment planning.     

Familial Dandy-Walker malformation and leukodystrophy

We report the first familial cases with two different types of posterior fossa cystic malformation and a leukodystrophic-like aspect on cerebral magnetic resonance imaging (MRI). The girl and her brother had severe encephalopathy, marked hypotonia, absent deep tendon reflexes, macrocrania, gigantism, and dysmorphic face and extremities. The girl had generalized seizures. The boy had unilateral cataract and bilateral optic atrophy. The parents were first cousins, suggesting autosomal recessive transmission. MRI showed Dandy-Walker variant in the girl, with cerebellar vermis hypoplasia and expansion of the cisterna magna, which communicated with the fourth ventricle. Her brother had mega cisterna magna communicating with the fourth ventricle and a normal cerebellum. The 2 children had abnormally high signal in the supratentorial white matter. Visual and auditory evoked potentials revelaed prolonged latencies. Motor and sensory conduction velocities were normal. Muscle and nerve biopsies were normal. Metabolic exploration demonstrated no abnormality.     

Cerebellar and brainstem involvement in familial juvenile nephronophthisis type I

We report on an 11-year-old boy with familial juvenile nephronophthisis type I associated with cerebellar ataxia and nystagmus, but not with ocular motor apraxia. An MRI revealed hypoplasia of the brainstem and vermis, and an enlargement of the fourth ventricle. A molecular genetic analysis demonstrated a homozygous deletion including the NPHP1 gene. These findings suggest that NPHP1 may play an important role in the normal development of the brainstem and the cerebellum as well as renal tissue.     

Familial cirsoid aneurysm of the scalp

One brother and one sister, of seven siblings, had cirsoid aneurysms of the occipital scalp with underlying skull defects and possible intracranial communication. Another sister had no gross scalp abnormality but radiographs of the skull revealed a small occipital bony defect. This is thought to be the first reported example of familial cirsoid aneurysm of the scalp.     

Decrease in cerebellar blood flow in patients with Friedreich’s ataxia: A TC-HMPAO SPECT study of three cases

Abstract

Three cases of Friedreich’s ataxia were submitted to diverse neuroradiological procedures in order to determine the extent of atrophic processes in the central nervous system. All patients underwent computerized-tomography scan, Magnetic Resonance Imaging, and HMPA-single Photon emission computerized tomography studies, focusing in cerebellar lobes. A slight atrophy was observed in the vermis and the cerebellar lobes with CT scan and MRI. In contrast a significant decrease in cerebellar blood flow was shown by TC-HMPAE SPECT study. The significance of these findings in understanding physiopathological mechanisms in Friedreich’s ataxia is discussed. [Neurol Res 1994; 16: 342-344]     

Spasticity and white matter abnormalities in adult phenylketonuria.

A 19 year old male with phenylketonuria (PKU) developed a spastic paparesis 8 months after stopping his restricted phenylalanine diet. CT and MRI showed abnormalities of the deep cerebral white matter, and visual evoked response latencies were prolonged. The spasticity gradually improved over several months after resuming the PKU diet. A repeat MRI scan was unchanged. His brother also had PKU and ceased dietary restrictions, but his only neurological abnormality was a slight increase in the deep tendon reflexes of the lower limbs. CT and MRI of his brain was normal. DNA analysis showed that both brothers were homozygous for the same PKU mutation. These patients demonstrate that reversible neurological signs may develop in patients with classic PKU after ceasing dietary restrictions and that these may be associated with abnormalities seen on neuro-imaging.     

Oculomotor abnormalities parallel cerebellar histopathology in autism

OBJECTIVE: To investigate cerebellar function in autism by measuring visually guided saccades. METHODS: A visually guided saccade task was performed by 46 high-functioning individuals with autism with and without delayed language acquisition, and 104 age and IQ matched healthy individuals. RESULTS: Individuals with autism had increased variability in saccade accuracy, and only those without delayed language development showed a mild saccadic hypometria. Neither autistic group showed a disturbance in peak saccade velocity or latency. CONCLUSIONS: The observed saccadic abnormalities suggest a functional disturbance in the cerebellar vermis or its output through the fastigial nuclei, consistent with reported cerebellar histopathology in autism. The pattern of mild hypometria and variable saccade accuracy is consistent with chronic rather than acute effects of cerebellar vermis lesions reported in clinical and non-human primate studies, as might be expected in a neurodevelopmental disorder. The different patterns of oculomotor deficits in individuals with autism with and without delayed language development suggest that pathophysiology at the level of the cerebellum may differ depending on an individual's history of language development.