A narrative review of risk factors and predictors for poor outcome and prolonged recovery after a mild traumatic brain injury.

Mild traumatic brain injuries (mTBI) are often caused by a blow to the head or a sudden jolt resulting in a wide range of physical, cognitive, and emotional temporary symptoms. Mild TBI diagnosis can be challenging and most commonly followed by post-concussion syndrome (PCS). When the symptoms are present for more than 3 months, prolonged post-concussive syndrome (PPCS) can be suspected. This review aims to identify and summarize the current status of the knowledge regarding the risk factors and predictors of the recovery from PCS and PPCS. A comprehensive search of the main scientific databases (PubMed, Web of Science, Embase, and Cochrane Library) was performed using keywords, such as: 'prolonged post-concussion syndrome', combined with 'risk factors', 'predictors', and 'outcomes'. Multiple studies reported more than one risk factor for PPCS development following mTBIs that were generally the results of sports-related concussions and car accidents. The most prevalent risk factor associated with PPCS was the female sex. Social factors/personality traits, anxiety, mental health disorders, or other health conditions from their past medical history, the occurrence of headache/migraines during TBI recovery, somatization, physical activity, and litigation were also reported to contribute to PPCS risk. An exhaustive approach is required to mitigate the risk of PPCS and to ensure optimal recovery after concussive events. However, larger prospective cohort studies evaluating patients that were examined and treated with standardized protocols could be needed to further validate these associations and mandate the highest risk factors for delayed recovery.

Understanding Functional Neurological Disorder: Recent Insights and Diagnostic Challenges.

Functional neurological disorder (FND), formerly called conversion disorder, is a condition characterized by neurological symptoms that lack an identifiable organic purpose. These signs, which can consist of motor, sensory, or cognitive disturbances, are not deliberately produced and often vary in severity. Its diagnosis is predicated on clinical evaluation and the exclusion of other medical or psychiatric situations. Its treatment typically involves a multidisciplinary technique addressing each of the neurological symptoms and underlying psychological factors via a mixture of medical management, psychotherapy, and supportive interventions. Recent advances in neuroimaging and a deeper exploration of its epidemiology, pathophysiology, and clinical presentation have shed new light on this disorder. This paper synthesizes the current knowledge on FND, focusing on its epidemiology and underlying mechanisms, neuroimaging insights, and the differentiation of FND from feigning or malingering. This review highlights the phenotypic heterogeneity of FND and the diagnostic challenges it presents. It also discusses the significant role of neuroimaging in unraveling the complex neural underpinnings of FND and its potential in predicting treatment response. This paper underscores the importance of a nuanced understanding of FND in informing clinical practice and guiding future research. With advancements in neuroimaging techniques and growing recognition of the disorder's multifaceted nature, the paper suggests a promising trajectory toward more effective, personalized treatment strategies and a better overall understanding of the disorder.

Cognitive Impairment following Mild Traumatic Brain Injury (mTBI): A Review.

Background: Mild Traumatic Brain Injury (mTBI) has been increasingly recognized as a public health concern due to its prevalence and potential to induce long-term cognitive impairment. We aimed to consolidate this observation by focusing on findings of neuropsychological assessments, neuroimaging, risk factors, and potential strategies for intervention to prevent and treat mTBI-associated cognitive impairments. Methods: A thorough search of PubMed, PsycINFO, and Embase databases was performed for studies published until 2024. Studies focusing on cognitive impairment after mTBI, with neurocognitive assessment as a primary outcome, were included. Results: We found consistent evidence of cognitive deficits, such as memory and attention impairments, and affected executive functions following mTBI. Neuroimaging studies corroborate these findings, highlighting structural and functional changes in the brain. Several risk factors for developing cognitive impairment post-mTBI were identified, including age, gender, genetics, and pre-existing mental health conditions. The efficacy of interventions, including cognitive rehabilitation and pharmaceutical treatment, varied across studies. Conclusions: Mild TBI can lead to significant long-term cognitive impairments, impacting an individual's quality of life. Further research is necessary to validate and standardize cognitive assessment tools post-mTBI, to elucidate the underlying neural mechanisms, and to optimize therapeutic interventions.

Inclusion body myositis. Genetics, biomarkers and muscle biopsy.

Sporadic inclusion body myositis is the most common idiopathic inflammatory myopathy over the age of 50, with a male-to-female ratio of 3:1. Symptoms onset before age of 60 occurs in 18-20% of patients, with a delay in diagnosis of 5 to 8 years.The classic clinical presentation of SIBM consists of proximal leg and distal arm weakness, and most commonly patients present early slowly progressive quadriceps weakness which leads to falls and to difficulties in climbing stairs, while less common the initial complaints refer to finger flexor weakness and atrophy, foot drop, or dysphagia, and rare presentations include prominent forearm weakness, sparing the quadriceps. The aetiopathogenesis of the disease remains unclear and despite some preliminary promising results, to the day there is no effective treatment.The diagnosis of SIBM is based on the clinical presentation and the histopathological findings in muscle biopsy, however increasing evidence on genetics and paraclinical biomarkers has recently come to light giving new insights on the pathogenesis, the diagnosis and the potential treatment of the disease. In the present study we aim to review the histopathological findings, genetics and blood biomarkers, and to review the role of muscle biopsy in the diagnosis of SIBM.

Chemical Composition, Antioxidant and Antiproliferative Activities of Taraxacum officinale Essential Oil.

Taraxacum officinale (TO) has been historically used for medicinal purposes due to its biological activity against specific disorders. To investigate the antioxidant and the antiproliferativepotential of TO essential oil in vitro and in vivo, the chemical composition of the essential oil was analyzed by GC-MS. The in vivo antioxidant capacity was assessed on liver and kidney homogenate samples from mice subjected to acetaminophen-induced oxidative stress and treated with TO essential oil (600 and 12,000 mg/kg BW) for 14 days. The in vitro scavenging activity was assayed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the reducing power methods. The cytotoxic effects against the HeLa cancer cell line were analyzed. The GC-MS analysis showed the presence of 34 compounds, 8 of which were identified as major constituents. The TO essential oil protected mice's liver and kidneys from acetaminophen-induced oxidative stress by enhancing antioxidant enzymes (catalase, superoxide dismutase, and glutathione) and lowering malondialdehyde levels. In vitro, the TO essential oil demonstrated low scavenging activity against DPPH (IC50 = 2.00 ± 0.05 mg/mL) and modest reducing power (EC50 = 0.963 ± 0.006 mg/mL). The growth of the HeLa cells was also reduced by the TO essential oil with an inhibition rate of 83.58% at 95 µg/mL. Current results reveal significant antioxidant and antiproliferative effects in a dose-dependent manner and suggest that Taraxacum officinale essential oil could be useful in formulations for cancer therapy.

Interactions between Sleep and Emotions in Humans and Animal Models.

Recently, increased interest and efforts were observed in describing the possible interaction between sleep and emotions. Human and animal model studies addressed the implication of both sleep patterns and emotional processing in neurophysiology and neuropathology in suggesting a bidirectional interaction intimately modulated by complex mechanisms and factors. In this context, we aimed to discuss recent evidence and possible mechanisms implicated in this interaction, as provided by both human and animal models in studies. In addition, considering the affective component of brain physiological patterns, we aimed to find reasonable evidence in describing the two-way association between comorbid sleep impairments and psychiatric disorders. The main scientific literature databases (PubMed/Medline, Web of Science) were screened with keyword combinations for relevant content taking into consideration only English written papers and the inclusion and exclusion criteria, according to PRISMA guidelines. We found that a strong modulatory interaction between sleep processes and emotional states resides on the activity of several key brain structures, such as the amygdala, prefrontal cortex, hippocampus, and brainstem nuclei. In addition, evidence suggested that physiologically and behaviorally related mechanisms of sleep are intimately interacting with emotional perception and processing which could advise the key role of sleep in the unconscious character of emotional processes. However, further studies are needed to explain and correlate the functional analysis with causative and protective factors of sleep impairments and negative emotional modulation on neurophysiologic processing, mental health, and clinical contexts.

Mini-Review on the Harlequin Syndrome-A Rare Dysautonomic Manifestation Requiring Attention.

Harlequin syndrome (HS) is a rare autonomic disorder. The causes and risk factors of the disease are not fully understood. Some cases of HS are associated with traumatic injuries, tumors, or vascular impairments of the head. Symptoms of HS can also occur in some autoimmune disorders, ophthalmic disorders, sleep disorders, and with certain organic lesions. In this context, a thorough review of the pathophysiology of HS in relation to neurological, ophthalmological, and dermatological conditions is necessary. In this mini-review, we aim to review the pathophysiological changes and underlying mechanisms in primary and secondary HS. Additionally, we discuss possible management approaches for patients with HS in light of the discussed pathological mechanisms. The main symptoms of HS that are correlated with autonomic nervous system impairments include sudden unilateral flushing of the face, neck, chest, and rarely arm, with concurrent contralateral anhidrosis. Despite reported co-occurring syndromes (such as cluster headaches), several studies have shown that HS could frequently overlap with other syndromes that are disruptive to the idiopathic nerve pathways. HS usually does not require any medical treatment. In some severe cases, symptomatic treatments could be needed. However, total symptomatic relief may not be achieved in many cases of HS. We therefore suggest an approach to comprehensive management of HS, which may lead to better long-term control of HS.

The role of neurofilament light chain in frontotemporal dementia: a meta-analysis.

Frontotemporal dementia (FTD) is the second most frequent dementia, after Alzheimer's, in patients under the age of 65. It encompasses clinical entities characterized by behavioral, language, and executive control dysfunction. Neurofilament light chain (NfL) is a new, non-disease specific, widely studied biomarker indicative of axonal injury and degeneration. Various studies have previously explored the role of NfL in the diagnostic process, monitoring, and prognosis of dementia. The current systematic review and meta-analysis include all the available data concerning the role of NfL in frontotemporal dementia and its use as a potential biomarker in differentiating patients with FTD from (a) healthy individuals, (b) Alzheimer's dementia, (c) Dementia with Lewy bodies, (d) Motor Neuron disease, (e) Parkinsonian syndromes, and (f) psychiatric disorders. We also analyze the utility of NfL in distinguishing specific FTD subgroups. Neurofilament light chain has a potential role in differentiating patients with frontotemporal dementia from healthy controls, patients with Alzheimer's dementia, and psychiatric disorders. Higher NfL levels were also noted in patients with semantic primary progressive aphasia (PPA) when compared with behavioral FTD and non-fluent PPA patients. Further studies exploring the use of NfL in frontotemporal dementia are needed.

Electroencephalogram in dementia with Lewy bodies: a systematic review.

Dementia with Lewy bodies (DLB) belongs to the spectrum of Lewy body dementia (LBD) that also encompasses Parkinson's disease dementia (PDD). It is a common neurodegenerative disorder characterized by memory decline, cognitive fluctuations, visual hallucinations, autonomic nervous system disturbance, REM sleep behavior disorder, and parkinsonism. Definite diagnosis can be established only through neuropathological confirmation of Lewy bodies' presence in brain tissue. Probable or possible diagnosis relies upon clinical features, imaging, polysomnography, and electroencephalogram (EEG) findings. Potential neurophysiological biomarkers for the diagnosis, management, and evaluation of treatment-response in DLB should be affordable and widely available outside academic centers. Increasing evidence supports the use of quantitative EEG (qEEG) as a potential DLB biomarker, with promising results in discriminating DLB from other dementias and in identifying subjects who are on the trajectory to develop DLB. Several studies evaluated the diagnostic value of EEG in DLB. Visual analysis and qEEG techniques have been implemented, showing a superiority of the last in terms of sensitivity and objectivity. In this systematic review, we attempt to provide a general synthesis of the current knowledge on EEG application in DLB. We review the findings from original studies and address the issues remaining to be further clarified.

A meta-analysis on the levels of VILIP-1 in the CSF of Alzheimer's disease compared to normal controls and other neurodegenerative conditions.

Alzheimer's disease (AD) is a progressing neurodegenerative disorder and the main cause of serious irreversible cognitive decline in elderly people. Visinin-like protein 1 (VILIP-1) is a member of the family of calcium-binding proteins and plays a crucial role in AD pathophysiology. Multiple studies have shown that CSF levels of VILIP-1 are increased in AD patients compared to normal controls, or other neurodegenerative conditions. We searched online databases for studies on the levels of VILIP-1 in the CSF of AD patients in comparison to normal controls, mild cognitive impairment (MCI) patients and Dementia with Lewy bodies (DLB) patients. A total of ten studies were used for the comparison between AD and controls, three studies for the comparison between AD and MCI, two studies for AD and DLB and two studies for the comparison between stable MCI and MCI progressed to AD. We found that VILIP-1 levels are significantly higher in AD compared to normal controls, but not to the other groups, and furthermore, they are significantly higher in patient with MCI progressed to AD, than in stable MCI patients.

Cognitive Status Epilepticus: Two Case Reports.

Cognitive status epilepticus is an uncommon form of focal status epilepticus presenting with a dysfunction of language, thinking or associated higher cortical functions. The absence of ictal manifestations can be misleading and delay a prompt diagnosis. Here we present two patients; one with amnesic and one with aphasic status epilepticus. Through these cases, we aim to highlight the value of EEG performance early in the diagnostic work-up and early antiepileptic drug initiation in cases where an epileptic disorder cannot be excluded.

Gray Matter Changes in Juvenile Myoclonic Epilepsy. A Voxel-Wise Meta-Analysis.

Background and Objectives. Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epileptic syndrome, with a genetic basis clinically identified by myoclonic jerks of the upper limbs upon awaking, generalized tonic-clonic seizures and less frequent absences. Although the brain magnetic resonance imaging (MRI) is by definition normal, computer-based Voxel-Based morphometry studies have shown a number of volumetric changes in patients with juvenile myoclonic epilepsy. Thus, the aim of the present Voxel-Wise Meta-Analysis was to determine the most consistent regional differences of gray matter volume between JME patients and healthy controls. Materials and Methods. The initial search returned 31 studies. After excluding reviews and studies without control groups or without detailed peak coordinates, 12 studies were finally included in the present meta-analysis. The total number of JME patients was 325, and that of healthy controls was 357. Results. Our study showed a statistically significant increase of the gray matter in the left median cingulate/paracingulate gyri, the right superior frontal gyrus, the left precentral gyrus, the right supplementary motor area and left supplementary motor area. It also showed a decrease in the gray matter volume in the left thalamus, and in the left insula. Conclusions. Our findings could be related to the functional deficits and changes described by previous studies in juvenile myoclonic epilepsy. In this way, the volumetric changes found in the present study could be related to the impaired frontal lobe functions, the emotional dysfunction and impaired pain empathy, and to the disrupted functional connectivity of supplementary motor areas described in JME. It additionally shows changes in the volume of the left thalamus, supporting the theory of thalamocortical pathways being involved in the pathogenesis of juvenile myoclonic epilepsy.

A Voxel-Wise Meta-Analysis on the Cerebellum in Essential Tremor.

Background and Objectives: Essential tremor is a chronic progressive neurological condition. The clinical presentation of essential tremor is heterogeneous and includes involuntary tremor on hands or arms and progressively on head, jaw, and voice. More extensive and complex symptoms may also be noticed in several patients. Many studies have been carried out to identify biomarkers to help the diagnosis, however, all the efforts have not shown any substantial results yet. Materials and Methods: Here, we aimed to perform a voxel-based meta-analysis using a dedicated cerebellar mask to clarify whether the results from the previous studies are robust and have any clinical significance. We included studies with a total of 377 essential tremor patients and 338 healthy control individuals. Results: A significant regional decrease in the volume of the gray matter was detected in the right cerebellar hemispheric lobule IV/V, and in the cerebellar vermic lobule IV/V. Conclusions: This is the first study focused on the cerebellum and using a specific cerebellar mask, which increases the sensitivity. It showed regional statistically significant changes that could not be seen in the whole-brain analysis.

YKL-40 as a Potential Biomarker for the Differential Diagnosis of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, associated with extensive neuronal loss, dendritic and synaptic changes resulting in significant cognitive impairment. An increased number of studies have given rise to the neuroinflammatory hypothesis in AD. It is widely accepted that AD brains show chronic inflammation, probably triggered by the presence of insoluble amyloid beta deposits and neurofibrillary tangles (NFT) and is also related to the activation of neuronal death cascade. In the present study we aimed to investigate the role of YKL-40 levels in the cerebrospinal fluid (CSF) in the diagnosis of AD, and to discuss whether there are further potential roles of this protein in the management and treatment of AD. We conducted an online search on PubMed, Web of Science, and the Cochrane library databases from 1990 to 2021. The quantitative analysis showed that the levels of YKL-40 were significantly higher in Alzheimer's disease compared to controls, to mild cognitive impairment (MCI) AD (MCI-AD) and to stable MCI. They were also increased in MCI-AD compared to stable MCI. The present study shows that the CSF levels of YKL-40 could be potentially used as a biomarker for the prognosis of mild cognitive impairment and the likelihood of progression to AD, as well as for the differential diagnosis between AD and MCI.

Serum BDNF Levels in Acute Stroke: A Systematic Review and Meta-Analysis.

Background and objectives: Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins. Low BDNF concentrations have been noted in patients with traditional cardiovascular disease risk factors and have been associated with the increased risk of stroke/transient ischemic attack (TIA). We aimed to study the correlation of BDNF serum levels with acute stroke severity and its potential role as a biomarker in predicting functional outcome. Materials and methods: We systematically searched PubMed, Web of Science, and the Cochrane database using specific keywords. The endpoints examined were the correlation of BDNF with functional outcome, the National Institute of Health stroke scale (NIHSS) measured at the acute phase, and stroke infarct volume. We also compared serum BDNF levels between stroke patients and healthy controls. Results: Twenty-six records were included from the initial 3088 identified. Twenty-five studies reported NIHSS and BDNF levels on the first day after acute stroke. Nine studies were further meta-analyzed. A statistically significant negative correlation between NIHSS and BDNF levels during the acute phase of stroke was noted (COR: -0.3013, 95%CI: (-0.4725; -0.1082), z = -3.01, p = 0.0026). We also noted that BDNF levels were significantly lower in patients with stroke compared to healthy individuals. Due to the heterogeneity of studies, we only conducted a qualitative analysis regarding serum BDNF and functional outcome, while no correlation between BDNF levels and stroke infarct volume was noted. Conclusions: We conclude that in the acute stroke phase, stroke severity is negatively correlated with BDNF levels. Concurrently, patients with acute stroke have significantly lower BDNF levels in serum compared to healthy controls. No correlations between BDNF and stroke infarct volume or functional outcome at follow-up were noted.

Alpha-synuclein Levels in the Differential Diagnosis of Lewy Bodies Dementia and Other Neurodegenerative Disorders: A Meta-analysis.

SUBJECTIVES: Lewy body dementia (LBD) is the second most common type of neurodegenerative dementia after Alzheimer disease (AD). It is characterized by the accumulation of Lewy bodies and Lewy neurites which are composed of aggregated phosphorylated alpha-synuclein, which is a presynaptic neuronal protein genetically and neuropathologically linked to Parkinson disease and to LBD. Alpha-synuclein is thought to contribute to LBD pathogenesis and to linked to disruption of cellular homeostasis and neuronal death, through effects on various intracellular targets, including synaptic function. METHODS: In the present study, we did a meta-analysis on the reliability of alpha-synuclein levels in the cerebrospinal fluid (CSF) for the discrimination between LBD and other neurodegenerative disorders including AD, Parkinson disease (PD) dementia, progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and frontotemporal dementia (FTD). RESULTS: CSF alpha-synuclein levels were significantly different in LBD compared with AD, but no statistical difference was found between LBD, and dementia in PD, MSA, PSP, and FTD. CONCLUSION: Alpha-synuclein levels in the CSF can be used for the discrimination between LBD and AD, but not LBD and other neurodegenerative disorders such as dementia in PD, MSA, FTD, and PSP.

A meta-analysis on CSF neurogranin levels for the diagnosis of Alzheimer's disease and mild cognitive impairment.

OBJECTIVE: Neurogranin is a postsynaptic protein involved in long-term potentiation and synaptic plasticity. Recent studies have shown increased neurogranin levels in the cerebrospinal fluid of Alzheimer's disease patients, and in patients with mild cognitive impairment. METHOD: We searched the online databases for studies on neurogranin cerebrospinal fluid levels in Alzheimer's disease, mild cognitive impairment and other neurodegenerative disorders, and we did a meta-analysis to clarify whether this can be a reliable biomarker for the diagnosis of Alzheimer's disease, and the discrimination from other disorders. RESULTS: The present meta-analysis showed that neurogranin CSF levels are significantly higher in AD patients compared to NC [SMD: 268.26, 95% CI (143.47, 393.04), Z = 4.21, P = 0.0001], MCI [SMD: 23.45 (15.97, 30.92), Z = 6.15, P < 0.00001], FTD [SMD: 1.91 (0.92, 2.89), Z = 3.80, P < 0.0001], but no significant difference was found between AD and LBD [SMD: 138.51 (- 14.92, 291.95), Z = 1.77, P = 0.08]. Comparison of stable MCI and MCI that progressed to AD showed significantly higher levels in the CSF of MCI patients who progressed to AD, compared to stable MCI patients [SMD: 230.84 (12.54, 449.14), Z = 2.07, P = 0.04]. Neurogranin can also be a useful biomarker for the differentiation MCI and NC, but not between MCI and FTD or LBD. CONCLUSION: Neurogranin could be added to the panel of existing biomarkers for a more accurate diagnosis and progress of AD and assessment of underlying pathological changes in the brain.

Mini-Review on Lipofuscin and Aging: Focusing on The Molecular Interface, The Biological Recycling Mechanism, Oxidative Stress, and The Gut-Brain Axis Functionality.

Intra-lysosomal accumulation of the autofluorescent "residue" known as lipofuscin, which is found within postmitotic cells, remains controversial. Although it was considered a harmless hallmark of aging, its presence is detrimental as it continually accumulates. The latest evidence highlighted that lipofuscin strongly correlates with the excessive production of reactive oxygen species; however, despite this, lipofuscin cannot be removed by the biological recycling mechanisms. The antagonistic effects exerted at the DNA level culminate in a dysregulation of the cell cycle, by inducing a loss of the entire internal environment and abnormal gene(s) expression. Additionally, it appears that a crucial role in the production of reactive oxygen species can be attributed to gut microbiota, due to their ability to shape our behavior and neurodevelopment through their maintenance of the central nervous system.

Neuroimaging and neuropathological findings in essential tremor.

Essential tremor is a chronic neurological syndrome of heterogenous clinical phenotypes and multiple etiologies. Numerous studies have been done in order to investigate the pathological, neuroimaging, physiological, and clinical features of essential tremor; however, a clear pathophysiological mechanism has not been identified. One of the brain structures has been extensively investigated at the macroscopic and the microscopic level in the cerebellum. In the present study, we aim to discuss the main neuroimaging and neuropathological changes of the cerebellum in essential tremor.

Cerebellar pathology in Alzheimer's disease.

Alzheimer's disease (AD) is one of the main causes of dementia in the western world. It is clinically characterized by memory impairment, deterioration of intellectual faculties and loss of professional skills. AD brains exhibit significant atrophy, predominantly in the temporal and parietal lobes, while light microscopy reveals deposition of senile plaques and neurofibrillary degeneration initially in the entorhinal cortex, the hippocampus, and in the acoustic and visual cortices, in the frontal lobe and the cerebellum in the advanced stages. Dendritic and spinal pathology, as well as loss of synapses are also key neuropathological features. The cerebellum is a critical part in the distributed neural circuits participating not only in motor function but also in autonomic, limbic and cognitive behaviours. Lesions of the motor cerebellum, mostly in lobules III-V in the anterior lobe and the secondary sensorimotor region in lobule VIII result in dysmetria of movement, however lesions of the cognitive and limbic cerebellum in the posterior lobe, represented in lobules VI, VIIA (including lobules VIIAf and VIIAt at the vermis, and crus I and crus II in the hemispheres) and VIIB, and possibly lobule IX, are followed by dysmetria in the realms of intellect and emotion. Cerebellar functional topography has been demonstrated by tract tracing studies in non-human primates and in physiological and behavioural studies in rodents, cats and monkeys. Further studies revealed the existence of a mosaic of intrinsic connectivity networks that match the topographically precise cerebrocerebellar connections, while topographic organization of cerebellum is also evident in task-based functional MRI in healthy controls, and in clinical neurology, neuropsychology and neuropsychiatry studies in patients with cerebellar lesions. Although the cerebellum has not been extensively studied in AD, recent studies have revealed evidence of a unique pathological pattern of the cerebellar cortex, including loss of Purkinje cells, synaptic alterations in the mossy fibres, granule cell dendrites, parallel fibres and Purkinje cell dendrites with substantial loss of dendritic spines, and considerable alterations in ultrathin sections.