Cerebellar Syndrome Research Articles

Chapter 8 - Cerebellum: From the identification of the cerebellar motor syndrome to the internal models

Cerebellar circuitry is topographically arranged in closed loops with the cerebral cortex. The three cornerstones of clinical ataxia have emerged from studies on connectional anatomy and from clinical/neuropsychological observations, leading to the definition of clinical syndromes encountered in daily practice: (a) the cerebellar motor syndrome (CMS), (b) the vestibulocerebellar syndrome (VCS), and (c) the cerebellar cognitive affective syndrome/Schmahmann syndrome (CCAS/SS). These syndromes are either isolated or coexist, depending on the underlying pathological process and its degree of extension within the cerebellum. Dysmetria is the core feature of cerebellar deficits, encompassing motor dysmetria (hypermetria, hypometria) in CMS, oculomotor dysmetria in VCS, and dysmetria of thought in CCAS/SS. The leading hypothesis is that dysmetria results from errors in building or maintaining internal models, which are inherent to predictive behavior. Errors in prediction would lead to clumsiness and incoordination of limbs, oculomotor impairments, and aberrant cognitive/affective behavior. The cerebellum is currently viewed as a learning machine enriched with multiple plasticity mechanisms, allowing the permanent adaptation to the external world by generating and maintaining predictive operations, from motor to cognitive, affective, emotional, and social operations essential for daily human life.

Multiple system atrophy

The article presents a progressive neurodegenerative disease - multisystem atrophy, characterized by a combination of autonomic failure and various motor disorders, including parkinsonism and/or cerebellar ataxia; etiopathogenetic factors and variants of the clinical picture are described. We describe own clinical observation of a 59-old patient with cerebellar and bulbar syndromes, parkinsonism, pyramidal insufficiency, cognitive deficits, and autonomic dysfunction. The differential diagnosis included a whole range of neurodegenerative and hereditary diseases: Parkinson's disease, vascular parkinsonism, progressive supranuclear palsy, spinocerebellar ataxia, FXTAS, mitochondrial encephalopathies. The moderate severity of parkinsonism and the significant predominance of cerebellar symptoms and autonomic dysfunction make this clinical case difficult to diagnose. However, based on the life and disease history, clinical picture and research methods, a diagnosis of multiple system atrophy, cerebellar type (cerebellar, autonomic, bulbar syndrome, parkinsonism, pyramidal insufficiency and moderate cognitive impairment) was established. Differential search in such patients is a difficult task and includes a whole range of neurodegenerative and hereditary diseases due to the similarity of individual clinical and neuroimaging features and, unfortunately, the limited availability of molecular genetic diagnostic methods. However, earlier diagnosis is necessary to focus in time on the development of a personalized approach to the management of each such patient, taking into account the rate of symptoms development and steady progression, in order to ensure the longest possible survival time with an acceptable level of quality of life.

Classical Infratentorial Superficial Siderosis Related to Spinal Abnormalities as a Cause of Cerebellar Cognitive Affective Syndrome.

Classical Infratentorial Superficial Siderosis Related to Spinal Abnormalities as a Cause of Cerebellar Cognitive Affective Syndrome.

THE IMPACT OF SELECTED NEUROPSYCHOLOGICAL BRAIN DYSFUNCTIONS ON THE CRIMINAL RESPONSIBILITY OF THE PERPETRATOR

Knowledge of clinical neuropsychology is of great importance in determining the possibility of holding the perpetrator criminally responsible and determining the scope of that responsibility. In the case of head injuries, the age of the brain, neurobiological and functional plasticity, brain resources, types and depth of dysfunction, as well as the assessment of the effects of current and planned therapy are important when assessing effects of determining responsibility. Findings in the field of clinical neuropsychology may be helpful especially in determining the subjective side (intention) of the perpetrator of the prohibited act, but above all – sanity (capacity). One of the grounds for declaring lack of criminal responsibility is “another disturbance of mental functions” (Article 31(1) Polish Criminal Code (CrC), which may include many neuropsychological conditions, such as frontal lobe syndromes, temporal lobe syndromes, frontotemporal disorders, temporal lobe epilepsy, limbic thalamus disorder, or cerebellar cognitive-affective syndrome. They cause cognitive or emotional deficits that may result in abolishing or limiting to a large extent the ability to recognize the meaning of an act or to control one’s own behavior. Certain neuropsychological findings may be important in determining that an act was committed under the influence of error, for example, in the case of agnosia – that is, the inability to recognize or interpret stimuli regardless of the channel. This text will mainly present selected neuropsychological deficits and their impact on the criminal responsibility of the perpetrator in the context of Article 31 Polish Criminal Code.

Primena magnetne rezonancije u dijagnostici najčešćih spinocerebelarnih ataksija

Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal dominant ataxias characterized by a dominantly progressive evolution of the cerebellar syndrome and other extra-cerebellar symptoms and signs. Today there are approximately 40 genetic SCAs and this review aims to describe the clinical picture and magnetic resonance imaging (MRI) findings of the most common SCA subtypes in Europe and Serbia. This is a group of polyglutamine diseases caused by mutations resulting from the expansion of the CAG repeats and accompanied by the loss of neural volume mainly of the cerebellum and the spinal cord. Magnetic resonance has a vital role in the diagnosis since it excludes structural damage as one of the potential causes of ataxia. In addition to this, the loss of volume, as demonstrated by MRI, serves as a biomarker that helps to monitor the natural progression of different subtypes of the disease. Typical findings in these MRI scans include cortico-cerebellar atrophy, spinal cord atrophy, olivopontocerebellar atrophy, and different combinations of the said atrophies. Unfortunately, there are no distinct pathognomonic MRI signs or combinations of signs to facilitate diagnosis. There are, however, similarities in the MRI findings of some of the SCA subtypes, especially at disease onset. The ability to differentiate one pattern of atrophy from another and observe other clinical characteristics can have an important role and can be of significant help in the diagnostic process.

The Entity of Cerebellar Mutism Syndrome: A Narrative Review Centered on the Etiology, Diagnostics, Prevention, and Therapeutic Options.

Cerebellar mutism syndrome (CMS), also known as posterior fossa syndrome, is an entity that entails a constellation of signs and symptoms which are recorded in a limited number of pediatric patients who have been operated on mainly for tumors involving the posterior cranial fossa, and more precisely, the region of the vermis. Medulloblastoma seems to constitute the most commonly recognized pathological substrate, associated with this entity. The most prevalent constituents of this syndrome are noted to be a, often transient, although protracted, language impairment, emotional lability, along with cerebellar and brainstem dysfunction. Apart from that, a definite proportion of involved individuals are affected by irreversible neurological defects and long-lasting neurocognitive impairment. A bulk of literature and evidence based on clinical trials exist, which reflect the continuous effort of the scientific community to highlight all perspectives of this complex phenomenon. There are several circumstances that intervene in our effort to delineate the divergent parameters that constitute the spectrum of this syndrome. In summary, this is implicated by the fact that inconsistent nomenclature, poorly defined diagnostic criteria, and uncertainty regarding risk factors and etiology are all constituents of a non-well-investigated syndrome. Currently, a preliminary consensus exists about the identification of a group of diagnostic prerequisites that are managed as sine qua non, in our aim to document the diagnosis of CMS. These include language impairment and emotional lability, as proposed by the international Board of the Posterior Fossa Society in their consensus statement. It is common concept that midline tumor location, diagnosis of medulloblastoma, younger age at diagnosis, and preoperatively established language impairment should be accepted as the most determinant predisposing conditions for the establishment of this syndrome. A well-recognized pathophysiological explanation of CMS includes disruption of the cerebellar outflow tracts, the cerebellar nuclei, and their efferent projections through the superior cerebellar peduncle. Despite the relative advancement that is recorded regarding the diagnostic section of this disease, no corresponding encouraging results are reported, regarding the available treatment options. On the contrary, it is mainly targeted toward the symptomatic relief of the affected individuals. The basic tenet of our review is centered on the presentation of a report that is dedicated to the definition of CMS etiology, diagnosis, risk factors, clinical presentation, and clinical management. Apart from that, an effort is made that attempts to elucidate the paramount priorities of the scientific forum, which are directed toward the expansion our knowledge in the era of diagnostics, prevention, and therapeutic options for patients suffering from CM, or who are at risk for development of this syndrome.

Gambling associated risk-taking decision in cerebellar ataxia

IntroductionPeople with cerebellar ataxia (CA) can develop impulsive and compulsive behaviors that significantly affect their and their family's quality of life. To further assess the decision-making process associated with these behaviors, we used the Iowa Gambling Task (IGT) to study people with CA. MethodsSixty individuals with CA and thirty age-matched controls were enrolled in the study to complete the IGT. No participants had a prior or comorbid neurologic or psychiatric disorder associated with impulsivity. IGT performance in each of the five 20-trial blocks was compared between groups and the progression of participants' performance was assessed with simple linear regression models. Subgroup analyses were performed with genetic and non-genetic CA cases. ResultsCA cases obtained significantly lower IGT total scores than controls (−5.30 ± 37.53 vs. 21.30 ± 37.37, p = 0.004). In addition, those with CA made riskier decisions throughout the task compared to controls. Although both CA and controls learned to make decisions with more favorable outcomes over the course of completing the IGT, CA participants never matched the controls' performance. IGT performance did not correlate with ataxia severity or depressive symptoms. ConclusionThe IGT may capture a unique behavioral symptom of CA. Future studies may help elucidate the mechanisms underlying impaired decision-making in CA and further the understanding of a broader spectrum of cerebellar cognitive affective syndrome.

Early and Aggressive Treatment May Modify Anti-Hu Associated Encephalitis Prognosis.

Anti-Hu encephalitis is a paraneoplastic syndrome in adults. In children, rare cases of anti-Hu encephalitis were reported mostly without underlying tumors and clinical outcome are usually severe. Here, we describe a 4-year-old girl who developed cerebellar syndrome with abnormal behavior. The brain magnetic resonance imaging showed several T2/fluid-attenuated inversion recovery bilateral brain lesions and autoimmune assessment showed positive anti-Hu antibodies. Computed tomography scan revealed ganglioneuroblastoma which was surgically removed 3 months after onset. Aggressive immunotherapy including dexamethasone, rituximab, and intravenous immunoglobulins were used and a marked neurological improvement soon after 9 months of onset was observed with the child being able to go back to school. The short delay between diagnosis and start of aggressive immunotherapy demonstrate the paramount importance of early diagnosis and early specific therapy after onset of symptoms.

A presurgical voxel-wise predictive model for cerebellar mutism syndrome in children with posterior fossa tumors

BackgroundThis study aimed to investigate cerebellar mutism syndrome (CMS)-related voxels and build a voxel-wise predictive model for CMS. MethodsFrom July 2013 to January 2022, 188 pediatric patients diagnosed with posterior fossa tumor were included in this study, including 38 from a prospective cohort recruited between 2020 and January 2022, and the remaining from a retrospective cohort recruited in July 2013-Aug 2020. The retrospective cohort was divided into the training and validation sets; the prospective cohort served as a prospective validation set. Voxel-based lesion symptoms were assessed to identify voxels related to CMS, and a predictive model was constructed and tested in the validation and prospective validation sets. ResultsNo significant differences were detected among these three data sets in CMS rate, gender, age, tumor size, tumor consistency, presence of hydrocephalus and paraventricular edema. Voxels related to CMS were mainly located in bilateral superior and inferior cerebellar peduncles and the superior part of the cerebellum. The areas under the curves for the model in the training, validation and prospective validation sets were 0.889, 0.784 and 0.791, respectively. ConclusionsSuperior and inferior cerebellar peduncles and the superior part of the cerebellum were related to CMS, especially the right side, and voxel-based lesion-symptom analysis could provide valuable predictive information before surgery.

Ataxia Rating Scales Reflect Patient Experience: an Examination of the Relationship Between Clinician Assessments of Cerebellar Ataxia and Patient-Reported Outcomes

Ataxia rating scales are observer administered clinical outcome assessments (COAs) of the cerebellar motor syndrome. It is not known whether these COAs mirror patient experience of their disease. Here we test the hypothesis that ataxia COAs are related to and reflect patient reported symptoms and impact of illness. A concept library of symptoms and activities impacted by ataxia was created by reviewing (a) concept elicitation data from surveys completed by 147 ataxia patients and 80 family members and (b) cognitive debrief data from focus groups of 17 ataxia patients used to develop the Patient Reported Outcome Measure of Ataxia. These findings were mapped across the items on 4 clinical measures of ataxia (SARA, BARS, ICARS and FARS). Symptoms reported most commonly related to balance, gait or walking, speech, tremor and involuntary movements, and vision impairment. Symptoms reported less frequently related to hand coordination, loss of muscle control, dizziness and vertigo, muscle discomfort or pain, swallowing, and incontinence. There was a mosaic mapping of items in the observer-derived ataxia COAs with the subjective reports by ataxia patients/families of the relevance of these items to their daily lives. Most COA item mapped onto multiple real-life manifestations; and most of the real-life impact of disease mapped onto multiple COA items. The 4 common ataxia COAs reflect patient reported symptoms and impact of illness. These results validate the relevance of the COAs to patients’ lives and underscore the inadvisability of singling out any one COA item to represent the totality of the patient experience.

A Woman With Kelch-like Protein-11 Encephalitis and Unmasked Metastatic Carcinoma

Objective To illustrate a case of a woman with rhombencephalitis with antibodies to Kelch-like protein-11 (KLHL11) and a metastatic carcinoma. Background KLHL11 encephalitis is an autoimmune paraneoplastic syndrome first described in 2019. The clinical presentation consists of a brainstem cerebellar syndrome with symptoms of hearing loss, diplopia, vertigo and ataxia. This entity has been mostly described in male patients with associated testicular seminomas. Few cases have been described in women. This is a case of a woman with a history of hysterectomy and oophorectomy with KLHL11 encephalitis and an associated aortocaval tumor. Design/Methods NA. Results The patient was a 62-year-old woman that presented to clinic with a 9-month history of vertigo, progressive bilateral sensorineural hearing loss, diplopia, oscillopsia, ataxia and bilateral tremor. Her MRI brain obtained 8 months after symptom onset showed T2 hyperintense lesions in the inferior cerebellar hemispheres and right medial hippocampus with mild contrast enhancement in these areas. Cerebral spinal fluid analysis showed a lymphocytic pleocytosis, elevated protein, and negative infectious work-up. She completed 5 days of intravenous methylprednisolone and continued a steroid taper. She noted mild to moderate improvement in tremors, gait, and diplopia after steroids. Her symptoms, however worsened as she tapered her steroid dose. Serum KLHL11 antibody levels were positive at a titer of 1:7680. Computed tomography of the chest, abdomen and pelvis did not reveal any evidence of malignancy. However, whole body proton emission tomography/computed tomography (PET CT) revealed a large hypermetabolic aortocaval mass soft tissue mass. A biopsy of the mass showed pathology consistent with a metastatic carcinoma of gynecologic origin for which the patient is undergoing chemotherapy with plans for possible tumor debulking. Conclusions This case highlights the importance of considering KLHL-11 encephalitis in female patients presenting with rhombencephalitis, and the need for adequate malignancy evaluation in this disorder.

Cerebellar mutism syndrome: From pathophysiology to rehabilitation.

Cerebellar mutism syndrome (CMS) is a common complication following surgical resection of childhood tumors arising in the posterior fossa. Alteration of linguistic production, up to muteness and emotional lability, generally reported at least 24h after the intervention, is the hallmark of post-operative CMS. Other associated traits include hypotonia and other cerebellar motor signs, cerebellar cognitive-affective syndrome, motor deficits from the involvement of the long pathways, and cranial neuropathies. Recovery usually takes 6 months, but most children are burdened with long-term residual deficits. The pathogenic mechanism is likely due to the damage occurring to the proximal efferent cerebellar pathway, including the dentate nucleus, the superior cerebellar peduncle, and its decussation in the mesencephalic tegmentum. Proven risk factors include brain stem invasion, diagnosis of medulloblastoma, midline localization, tumor size, invasion of the fourth ventricle, invasion of the superior cerebellar peduncle, left-handedness, and incision of the vermis. Currently, rehabilitation is the cornerstone of the treatment of patients with cerebellar mutism syndrome, and it must consider the three main impaired domains, namely speech, cognition/behavior, and movement.

Postoperative MRI features of cerebellar mutism syndrome: a retrospective cohort study.

In this study, the authors aimed to investigate the relationship between postoperative MRI features and cerebellar mutism syndrome. A retrospective cohort of patients who underwent tumor resection from July 2013 to March 2021 for midline posterior fossa tumors was investigated. All patients were followed up at least once. Clinical data were extracted from medical records and follow-up databases. Two neuroradiologists independently reviewed preoperative and postoperative MRI. Univariable and multivariable analyses were performed to compare the postoperative cerebellar mutism syndrome (pCMS) and non-pCMS groups. Correlation analysis was performed using the Spearman correlation coefficient analysis. Of 124 patients, 47 (37.9%) developed pCMS. The median follow-up duration was 45.73 (Q1: 33.4, Q3: 64.0) months. The median duration of mutism was 45 days. The median tumor size was 48.8 (Q1: 42.1, Q3: 56.8) mm. In the univariable analysis, abnormal T2-weighted signal of the left dentate nucleus (DN) (74.5% in the pCMS group vs 36.4% in the non-pCMS group, p < 0.001), right DN (83.0% vs 40.3%, p < 0.001), left superior cerebellar peduncle (SCP) (74.5% vs 27.3%, p < 0.001), right SCP (63.8% vs 23.4%, p < 0.001), left middle cerebellar peduncle (MCP) (51.1% vs 26.0%, p = 0.008), and right MCP (61.7% vs 26.0%, p < 0.001); male sex (83.0% vs 45.5%, p < 0.001); vermis 3 impairment (49.4% vs 19.1%, p = 0.002); solid tumor (91.5% vs 72.7%, p = 0.022); and hydrocephalus (72.3% vs 45.5%, p = 0.006) were more frequent in the pCMS group than in the non-pCMS group. Multivariable logistic analysis showed that male sex (adjusted OR 4.08, p = 0.010) and the cerebro-cerebellar circuit score of T2-weighted images (adjusted OR 2.15, p < 0.001) were independent risk factors for pCMS. The cerebro-cerebellar circuit score positively correlated with the duration of mutism. In Cox regression analysis, the cerebro-cerebellar integrated circuit injury score of T2 (adjusted HR 0.790, 95% CI 0.637-0.980; p = 0.032) and injury of vermis 3 (adjusted HR 3.005, 95% CI 1.197-7.547; p = 0.019) were independently associated with the duration of mutism. Male sex and cerebro-cerebellar circuit damage are independent risk factors for pCMS. The cerebro-cerebellar circuit score indicates the duration of mutism.

Anti-Yo Paraneoplastic Cerebellar Degeneration and Breast Cancer: A Long Survival of Persistent Cerebellar Syndrome

Paraneoplastic neurological syndromes (PNS) occur in 1–3% of all cancer patients with several cancer-related neurologic diseases involving any part of the nervous system. Paraneoplastic cerebellar degeneration (PCD) is a specific type of PNS characterized by sub-acute cerebellar syndrome with trunk and limb ataxia, dysarthria, diplopia, and vertigo. We report herein the case of a 70-year-old female patient with cerebellar symptoms and transient anti-Yo antibody PCD positivity manifested three years after a breast cancer diagnosis who is currently neurologically stable after an extended follow-up.

Erratum: Childhood-Onset Neurodegeneration with Cerebellar Atrophy Syndrome: Severe Neuronal Degeneration and Cardiomyopathy with Loss of Tubulin Deglutamylase Cytosolic Carboxypeptidase 1

Erratum: Childhood-Onset Neurodegeneration with Cerebellar Atrophy Syndrome: Severe Neuronal Degeneration and Cardiomyopathy with Loss of Tubulin Deglutamylase Cytosolic Carboxypeptidase 1

NCMP-14. NEUROTOXICITY AFTER A SINGLE CYCLE OF INTRAVENOUS CYTARABINE

Abstract Cytarabine neurotoxicity is well-documented, typically occurring after intrathecal treatment or a cumulative systemic dose of 36 g/m2. Encephalopathy, myelopathy, and acute cerebellar syndrome have all been described, with risk factors including advanced age and renal dysfunction. Here, we report a case of acute cerebellar syndrome after a single cycle of intravenous cytarabine 3 g/m2. This 65 year old man with history of chronic kidney disease (baseline creatinine 2.0 mg/dL) and primary central nervous system lymphoma had unconfirmed complete response after induction therapy with rituximab, methotrexate, and vincristine. Methotrexate was dosed between 1 -2 g/m2 due to renal dysfunction and delayed clearance. Given patient’s performance status and comorbidities, high-dose cytarabine consolidation was chosen. He received 3 g/m2 intravenously on days 1 and 2 of a 28-day cycle. On day 5, he developed acute truncal ataxia and was no longer able to sit or stand unsupported. He then presented to the emergency department on day 8 with persistent symptoms. Vital signs showed mild hypertension without orthostatic hypotension. Neurologic exam revealed postural instability, titubation, and inability to maintain seated posture with eyes closed. He had no dysmetria on finger-nose or heel-shin testing. Blood values were notable only for an elevated creatinine of 2.1 mg/dL. CT head revealed no acute pathology. MRI brain showed no infarct or recurrent disease. He was discharged home and symptoms resolved by day 10. Given clinical syndrome of truncal ataxia shortly after cytarabine, we diagnosed cytarabine-related neurotoxicity. Further cycles of consolidation were withheld for close observation. While cytarabine-related neurotoxicity is more common after an increased cumulative dose, it can occur after only a single cycle of 3 g/m2. Our patient’s age and baseline renal dysfunction likely predisposed him. Cytarabine dose-reduction can be considered in patients with these risk factors.

A taxonomy for brainstem cavernous malformations: subtypes of pontine lesions. Part 1: basilar, peritrigeminal, and middle peduncular.

Brainstem cavernous malformations (BSCMs) are complex, difficult to access, and highly variable in size, shape, and position. The authors have proposed a novel taxonomy for pontine cavernous malformations (CMs) based upon clinical presentation (syndromes) and anatomical location (findings on MRI). The proposed taxonomy was applied to a 30-year (1990-2019), 2-surgeon experience. Of 601 patients who underwent microsurgical resection of BSCMs, 551 with appropriate data were classified on the basis of BSCM location: midbrain (151 [27%]), pons (323 [59%]), and medulla (77 [14%]). Pontine lesions were then subtyped on the basis of their predominant surface presentation identified on preoperative MRI. Neurological outcomes were assessed according to the modified Rankin Scale, with a score ≤ 2 defined as favorable. The 323 pontine BSCMs were classified into 6 distinct subtypes: basilar (6 [1.9%]), peritrigeminal (53 [16.4%]), middle peduncular (MP) (100 [31.0%]), inferior peduncular (47 [14.6%]), rhomboid (80 [24.8%]), and supraolivary (37 [11.5%]). Part 1 of this 2-part series describes the taxonomic basis for the first 3 of these 6 subtypes of pontine CM. Basilar lesions are located in the anteromedial pons and associated with contralateral hemiparesis. Peritrigeminal lesions are located in the anterolateral pons and are associated with hemiparesis and sensory changes. Patients with MP lesions presented with mild anterior inferior cerebellar artery syndrome with contralateral hemisensory loss, ipsilateral ataxia, and ipsilateral facial numbness without cranial neuropathies. A single surgical approach and strategy were preferred for each subtype: for basilar lesions, the pterional craniotomy and anterior transpetrous approach was preferred; for peritrigeminal lesions, extended retrosigmoid craniotomy and transcerebellopontine angle approach; and for MP lesions, extended retrosigmoid craniotomy and trans-middle cerebellar peduncle approach. Favorable outcomes were observed in 123 of 143 (86%) patients with follow-up data. There were no significant differences in outcomes between the 3 subtypes or any other subtypes. The neurological symptoms and key localizing signs associated with a hemorrhagic pontine subtype can help to define that subtype clinically. The proposed taxonomy for pontine CMs meaningfully guides surgical strategy and may improve patient outcomes.

Highly asymmetrical distribution of muscle wasting correlates to the heteroplasmy in a patient carrying a large-scale mitochondrial DNA deletion: a novel pathophysiological mechanism for explaining asymmetry in mitochondrial myopathies

Mitochondrial diseases are a heterogeneous group of pathologies, caused by missense mutations, sporadic large-scale deletions of mitochondrial DNA (mtDNA) or mutations of nuclear maintenance genes. We report the case of a patient in whom extended muscle pathology, biochemical and genetic mtDNA analyses have proven to be essential to elucidate a unique asymmetrical myopathic presentation. From the age of 34 years on, the patient has presented with oculomotor disorders, right facial peripheral palsy and predominantly left upper limb muscle weakness and atrophy. By contrast, he displayed no motor weakness on the right hemi-body, and no sensory symptoms, cerebellar syndrome, hypoacusis, or parkinsonism. Cardiac function was normal. CK levels were elevated (671 UI/L). Electroneuromyography (ENMG) and muscle MRI showed diffuse myogenic alterations, more pronounced on the left side muscles. Biopsy of the left deltoid muscle showed multiple mitochondrial defects, whereas in the right deltoid, mitochondrial defects were much less marked. Extended mitochondrial biochemical and molecular workup revealed a unique mtDNA deletion, with a 63.4% heteroplasmy load in the left deltoid, versus 8.1% in the right one. This case demonstrates that, in mitochondrial myopathies, heteroplasmy levels may drastically vary for the same type of muscle, rising the hypothesis of a new pathophysiological mechanism explaining asymmetry in hereditary myopathies.

Adult's Medulloblastoma

Background and Objectives: Medulloblastoma are a highly malignant tumor of the central nervous system, very frequent in the childhood, but remains rare in adulthood. This study aims to analyze the frequency, clinical and therapeutic aspects of adults medulloblastomas. Methods: We retrospectively analyzed the data from the record of adult’s patients treated for medulloblastoma between between January 2000 and December 2015 in in the Radiation oncology department of the Ibn Rochd University Hospital Center. Results: The average age was 27,96 years (Range: 20-53 years). The sex ratio M/F was 4 with a clear male predominance. The most common symptom was intracranial hypertension, which was present in 22 patients, followed by headaches and cerebellar syndrome which were present in 9 patients. The tumor was mostly located in the cerebellar hemispheres with an average size of 5,75 cm. One patient had pulmonary metastasis at the time of diagnosis. Twenty-four patients had a surgical resection. Complete resection was performed in 13 patients. Thus, twenty-one patients have received craniospinal irradiation with a dose of 36 Gy followed by a boost in the posterior fossa with a total dose of 54-56 Gy. Twelve patients have received Chemotherapy. Six patients are still alive. Survival rates were 50% at 3 years, 35% at 5 years, and 30% at 10 years. Conclusion: Medulloblastoma is a devastating disease with a bad prognosis. The clinical presentation is variable and the management is multidisciplinary. Radiotherapy treatment with or without Chemotherapy play an important role in the control of the disease and recurrences avoidance. Our study illustrates the importance of treatment by radiation.

An atypical course of a 71-year old man with right arm weakness and ataxia: Expert commentary

Dr Khemani and colleagues have presented a diagnostically challenging case of a sporadic, adult onset ataxia (SAOA) syndrome resembling Multiple System Atrophy cerebellar type (MSA-C), with an atypical presentation of focal amyotrophy, eventually diagnosed as spinocerebellar ataxia type 3 (SCA3) [ [1] Khemani P. Elliott M. Levine T. An Atypical Clinical Course of a 71-Year-Old Man with Right Arm Weakness and Ataxia. Parkinsonism Relat Disord, 2022 Abstract Full Text Full Text PDF Scopus (0) Google Scholar ]. The patient had presented elsewhere three years prior, with a Miller Fisher syndrome (MFS) associated with an elevated antiGQ1b antibody titer. However, as the patient had become wheelchair bound over the subsequent three years, the initial diagnosis of MFS is perhaps questionable. When evaluating ataxic disorders, it is important to establish the disease onset and course accurately. As the patient had a progressive cerebellar syndrome, the possible causes could be categorized broadly as: primary autoimmune (paraneoplastic or non-paraneoplastic); or neurodegenerative (sporadic or genetic). Primary autoimmune cerebellar ataxia encompassing paraneoplastic ataxia syndromes, and immune-mediated ataxias (gluten ataxia and anti-GAD65 ataxia) may present insidiously, with accumulating disability especially if timely and appropriate immunosuppressive therapies are not instituted [ [2] Hadjivassiliou M. Graus F. Honnorat J. Jarius S. Titulaer M. Manto M. Hoggard N. Sarrigiannis P. Mitoma H. Diagnostic criteria for primary autoimmune cerebellar ataxia-guidelines from an international task force on immune-mediated cerebellar ataxias. Cerebellum. 2020; 19: 605-610 Crossref PubMed Scopus (35) Google Scholar ].