Longitudinal assessment of blepharospasm severity in patients with long disease duration.

INTRODUCTION: Blepharospasm (BSP) represents one of the most common idiopathic adult-onset dystonia. A few longitudinal observations indicated progression and worsening of BSP severity within 16 years of onset. Information is lacking about the trend of BSP severity in the later stages of the disease. METHODS: The study comprised 15 women and 3 men that underwent a standardized video protocol at two time points: 14 ± 9 years after BSP onset and 11 ± 2 years later. BSP severity was rated by the Blepharospasm Severity Rating Scale (BSRS). Two independent observers reviewed 36 videos in a pseudo-randomized order, yielding satisfactory agreement. RESULTS: Mean total severity score was 7.6 ± 3.9 years at baseline, 6.4 ± 2.5 at the last examination (p = 0.14). The last video examination showed a stable BSRS score in 14/18 patients, while the score of 4 patients decreased by two points or more, due to disappearance (n.3) or reduction (n.1) of prolonged spasms with complete rim closure. Over the long term, the BoNT dosage increased in those who improved, but remained stable in the other patients. On follow-up examination, dystonia spread to the lower face or neck in two new patients. No significant correlations emerged between disease duration and BSP severity. The presence of sensory trick significantly correlated with disease duration but not with BSP severity. DISCUSSION: This study provides novel information on the long-term prognosis in patients with idiopathic BSP, showing that severity of BSP may not worsen in the later stages of the disease.

Percutaneous gastrostomy, mechanical ventilation and survival in amyotrophic lateral sclerosis : an observational study in an incident cohort.

OBJECTIVE: To analyze disease-modifying effects of percutaneous endoscopic gastrostomy (PEG) insertion for supporting nutrition, noninvasive ventilation (NIV), and tracheostomy-assisted ('invasive') ventilation (TIV) in amyotrophic lateral sclerosis (ALS). METHODS: We retrospectively analyzed survival in a large population-based incident cohort that was prospectively followed up in our center. Analysis considered several known ALS-related prognostic variables. RESULTS: In this population, PEG and NIV in multivariable analysis significantly correlated to survival as computed by disease onset to death/tracheostomy. NIV was associated with better survival while PEG was associated with reduced survival. Other independent prognostic factors were age at ALS onset, diagnostic delay, and flail arm/leg and pure upper motor neuron (PUMN) phenotypes. The length of survival after TIV was significantly associated with age at ALS onset (inverse correlation) whereas other variables did not. The length of survival after TIV correlated to age at ALS onset in such a way that each additional year of age at ALS onset decreased survival by about 0.7 months. Patients who underwent both TIV and NIV did not experience a better survival than those who underwent TIV alone. CONCLUSION: The lack of effect of enteral nutrition on ALS survival probably reflected the timing of PEG insertion in patients with more severe disease. By contrast, patients who used mechanical ventilation had an increased overall survival compared with non-ventilated ones. The study also provided new information showing that the combined use of NIV and TIV did not may prolong ALS survival as compared to TIV alone.

Oromandibular dystonia: from onset to spread a multicenter italian study.

BACKGROUND: Detailed information about the epidemiological and phenomenological differences among the aetiological subtypes of oromandibular dystonia (OMD) is lacking. Moreover, the OMD tendency to spread to other body sites has never been investigated. AIM: To compare the main demographic and clinical features of OMD in different aetiological groups and assess the risk of spread. MATERIALS AND METHODS: We retrospectively analysed data from patients contained in the Italian Dystonia Registry. The risk of spread was assessed by Kaplan Meyer curves and Cox regression analysis. RESULTS: The study included 273 patients (175 women) aged 55.7 years (SD 12.7) at OMD onset. Female predominance was observed. Idiopathic dystonia was diagnosed in 241 patients, acquired dystonia in 22. In 50/273 patients, dystonia started in the oromandibular region (focal OMD onset); in 96/273 patients the onset involved the oromandibular region and a neighbouring body site (segmental/multifocal OMD onset); and in 127/273 patients OMD was a site of spread from another body region. Sensory trick (ST) and positive family history predominated in the idiopathic group. No dystonia spread was detected in the acquired group, whereas spread mostly occurred within the first five years of history in 34% of the focal OMD onset idiopathic patients. Cox regression analysis revealed ST as a significant predictor of spread (HR, 12.1; 95% CI, 2.5 - 18.8; P = 0.002). CONCLUSION: This large study provides novel information about the clinical phenomenology of idiopathic and acquired OMD. We pointed out a possible role of oestrogens in favouring dystonia development. Moreover, we described for the first time the association between ST and dystonia spread, revealing possible common pathophysiological mechanisms. Our findings may be suggested as a referral point for future pathophysiological and therapeutic studies on OMD.

Does sex influence the natural history of idiopathic adult-onset dystonia?

BACKGROUND: Several earlier studies showed a female predominance in idiopathic adult-onset dystonia (IAOD) affecting the craniocervical area and a male preponderance in limb dystonia. However, sex-related differences may result from bias inherent to study design. Moreover, information is lacking on whether sex-related differences exist in expressing other dystonia-associated features and dystonia spread. OBJECTIVE: To provide accurate information on the relationship between sex differences, motor phenomenology, dystonia-associated features and the natural history of IAOD. METHODS: Data of 1701 patients with IAOD from the Italian Dystonia Registry were analysed. RESULTS: Women predominated over men in blepharospasm, oromandibular, laryngeal and cervical dystonia; the sex ratio was reversed in task-specific upper limb dystonia; and no clear sex difference emerged in non-task-specific upper limb dystonia and lower limb dystonia. This pattern was present at disease onset and the last examination. Women and men did not significantly differ for several dystonia-associated features and tendency to spread. In women and men, the absolute number of individuals who developed dystonia tended to increase from 20 to 60 years and then declined. However, when we stratified by site of dystonia onset, different patterns of female-to-male ratio over time could be observed in the various forms of dystonia. CONCLUSIONS: Our findings provide novel evidence on sex as a key mediator of IAOD phenotype at disease onset. Age-related sexual dimorphism may result from the varying exposures to specific age-related and sex-related environmental risk factors interacting in a complex manner with biological factors such as hormonal sex factors.

Point prevalence of epilepsy in dementia: A "real-world" estimate.

OBJECTIVE: Several studies have demonstrated a higher frequency of seizures and epilepsy in Alzheimer's disease and other forms of dementia as compared with healthy elderly individuals. However, incidence and prevalence of epilepsy in the general population of dementia are unknown since most previous studies were performed in secondary-tertiary referral centres. In addition, all prior studies but one provided "period" rather than "point" prevalence estimates. METHODS: We assessed point prevalence estimate of epileptic manifestations requiring antiepileptic medication in patients Alzheimer's disease, vascular dementia, and fronto-temporal dementia from a secondary clinical setting. RESULTS: Point prevalence estimates were 6.4% (95% CI: 1.5 to 11.3) in Alzheimer's disease, 8.9% (95% CI: 1.4 to 16.4), in vascular dementia, and 6% (95% CI: 1.3 to 10.7) in fronto-temporal dementia, rates that were greater than those observed in the healthy elderly population. Regardless of the etiology of dementia, epilepsy was characterized by unprovoked seizures that lacked distinguishing clinical features. SIGNIFICANCE: These findings support epilepsy as part of the spectrum of dementia. The similar point prevalence of definite epilepsy requiring AED treatment in Alzheimer's disease and non Alzheimer dementias raised the possibility of similar underlying mechanism of epileptogenesis. Although this was not a population-based study, accurate point prevalence data from clinic setting would be important to better define the burden of epilepsy in dementia and the demands on health services to manage the condition.

Epidemiology of seropositive myasthenia gravis in Sardinia: A population-based study in the district of Sassari.

INTRODUCTION/AIMS: The global incidence and prevalence of myasthenia gravis (MG) range between 6-31/million and 10-37/100,000, respectively. Sardinia is a high-risk region for different immune-mediated disorders, but the epidemiology of MG remains unclear. We determined the epidemiology of MG with acetylcholine receptor (AChR)-immunoglobulin G (IgG) and muscle-specific tyrosine kinase (MuSK)-IgG in the district of Sassari (North-Western Sardinia; population, 325,288). METHODS: From the laboratory of the University Hospital of Sassari (reference for AChR/MuSK-IgG testing in Sardinia since 1998) and the main neurology units in Sardinia, we retrospectively identified MG patients with (1) AChR-IgG and/or MuSK-IgG positivity by radioimmunoprecipitation assay; and (2) residency in the district of Sassari. Incidence (January 2010-December 2019) and prevalence (December 31, 2019) were calculated. RESULTS: A total of 202 patients were included (incident, 107; prevalent, 180). Antibody specificities were AChR (n = 187 [93%]) and MuSK (n = 15 [7%]). The crude MG incidence (95% confidence interval) was 32.6 (26.8-39.2)/million, while prevalence was 55.3 (47.7-63.9)/100,000. After age-standardization to the world population, incidence decreased to 18.4 (14.3-22.5)/million, while prevalence decreased to 31.6 (26.1-37.0)/100,000. Among incident cases, age strata (years) at MG onset were: <18 (2%), 18-49 (14%), 50-64 (21%), and ≥65 (63%). DISCUSSION: Sardinia is a high-risk region for MG, with a prevalence that exceeds the European threshold for rare disease. Identification of the environmental and genetic determinants of this risk may improve our understanding of disease pathophysiology.

Does thyroid diseases contribute to the natural history of idiopathic adult-onset dystonia? Data from the Italian Dystonia Registry.

A few earlier observations and recent controlled studies pointed to the possible contribution of thyroid diseases in idiopathic adult-onset dystonia (IAOD). The aim of this study was to investigate the association between thyroid status and clinical characteristics of IAOD, focusing on dystonia localization, spread, and associated features such as tremors and sensory tricks. Patients were identified from those included in the Italian Dystonia Registry, a multicentre dataset of patients with adult-onset dystonia. The study population included 1518 IAOD patients. Patients with hypothyroidism and hyperthyroidism were compared with those without any thyroid disease. In the 1518 IAOD patients, 167 patients (11%; 95% CI 9.5-12.6%) were diagnosed with hypothyroidism and 42 (2.8%; 95% CI 1.99-3.74) with hyperthyroidism. The three groups were comparable in age at dystonia onset, but there were more women than men in the groups with thyroid disease. Analysing the anatomical distribution of dystonia, more patients with blepharospasm were present in the hyperthyroidism group, but the difference did not reach statistical significance after the Bonferroni correction. The remaining dystonia-affected body sites were similarly distributed in the three groups, as did dystonia-associated features and spread. Our findings provided novel information indicating that the high rate of thyroid diseases is not specific for any specific dystonia subpopulation and does not appear to influence the natural history of the disease.

Are Cognitive Symptoms Part of the Phenotypic Spectrum of Idiopathic Adult-Onset Dystonia? Summary of Evidence from Controlled Studies.

BACKGROUND: Cognitive dysfunction has been reported in idiopathic adult-onset dystonia (IAOD), but whether this is a primary or secondary component of the disorder remains uncertain. OBJECTIVE: Here, we aimed to analyze the key domains of abnormal cognitive performance in IAOD and whether this is associated with motor or mood changes. METHODS: Article selection for our critical review was guided by PRISMA guidelines (mesh terms "dystonia" and "cognitive," publication period: 2000-2022). Only peer-reviewed, English-language original case-control studies involving patients with IAOD who were not exposed to dopamine- or acetylcholine-modulating agents and validated cognitive assessments were included. RESULTS: Abstract screening ultimately yielded 22 articles for full-text review and data extraction. A greater proportion of studies (17 of 22, 82%) reported abnormal cognitive performance in IAOD. Most of these studies focused on blepharospasm (BSP) and cervical dystonia (10 and 14, respectively). Most studies reporting cognitive impairment (11 of 17) identified multidomain impairment in cognition. Executive functions were the domain most frequently explored (14 of 22 studies), 79% of which detected worse performance in people with dystonia. Results related to other domains were inconclusive. Cognitive abnormalities were independent of motor symptoms in most studies (7 of 12) that explored this relationship and independent of mood status in all 8 that investigated this. CONCLUSIONS: Within IAOD, cognitive dysfunction (in particular, executive dysfunction) has been documented mainly in BSP and cervical dystonia. More comprehensive testing is warranted to assess abnormalities in other domains and in other forms of IAOD, as well as to evaluate longitudinal progression of cognitive disturbances in this condition.

Disease survival and progression in TARDBP ALS patients from Sardinia, Italy.

BACKGROUND: Common genes implicated in amyotrophic lateral sclerosis (ALS) development may also influence its progression rate. The C9orf72 mutations featured a faster progression rate while the European SOD1 mutations were associated with a slower progression. In this study, we assessed the relationship between TARDBP and ALS progression/survival. METHODS: ALS incident patients (2010-2019) were diagnosed by El Escorial revised criteria and staged over the disease course by the King's staging system. Disease progression was analysed by Kaplan-Meier survival curves and Cox regression models, with survival measured from symptom onset to death/tracheostomy or censor date. RESULTS: The study population included 76 patients carrying TARDBP mutations (A382T/G295S), 28 patients carrying the C9orf72 GGGGCC expansion, and 158 patients who had no evidence of causative genetic mutations (nmALS group). TARDBP patients reached death/tracheostomy later than C9orf72 and nmALS patients, independently of possible prognostic indicators (sex, age at ALS onset, diagnostic delay, phenotype at onset, and family history of ALS). On King's staging, the time elapsed between disease onset (King's stage 1) and involvement of the second body region (King's stage 2B) was similar in TARDBP and nmALS patients but longer in TARDBP than in C9orf72 patients. TARDBP patients reached King's stages 3 and 4 later than C9orf72 and nmALS patients. CONCLUSIONS: TARDBP patients have a better survival/prognosis than C9orf72-positive and nmALS patients. King's staging also suggested that the higher survival rate and the slower progression associated with the TARDBP mutation could mainly be attributed to the longer time elapsed between King's stages 2B to 3.

Spatial clustering of amyotrophic lateral sclerosis in Sardinia, Italy: The contribution of age, sex, and genetic factors.

INTRODUCTION/AIMS: Several microgeographic clusters of higher/lower incidence of amyotrophic lateral sclerosis (ALS) have been identified worldwide. Differences in the distribution of local factors were proposed to explain the excess ALS risk, whereas the contribution of known genetic/epigenetic factors remains unclear. The aim is to identify restricted areas of higher risk in Sardinia and to assess whether age, sex, and the most common causative genetic mutations in Sardinia (C9orf72 and TARDBP mutations) contributed to the variation in the ALS risk. METHODS: We performed an ad hoc analysis of the 10-y population-based incident cohort of ALS cases from a recent study of a large Sardinian area. Cluster analysis was performed by age- and sex-adjusted Kulldorff's spatial scan statistic. RESULTS: We identified a statistically significant cluster of higher ALS incidence in a relatively large area including 34 municipalities and >100,000 individuals. The investigated genetic mutations were more frequent in the cluster area than outside. Regardless of the genetic mutations, the excess of ALS risk was significantly associated with either sex or with age ≥ 65 y. Finally, an additive interaction between older age and male sex contributed to the excess of ALS risk in the cluster area but not outside. DISCUSSION: Our analysis demonstrated that known genetic factors, age, and sex may contribute to microgeographic variation in ALS incidence. The significant additive interaction between older age and male sex we found in the high-incidence cluster could suggest the presence of a third factor connecting the analyzed risk factors.

Increasing prevalence 2015-2019 of amyotrophic lateral sclerosis in Sardinia, Italy.

BACKGROUND: While amyotrophic lateral sclerosis (ALS) incidence has increased during the last decades, structured evidence on increased prevalence is lacking. After reporting a significant yearly increase of ALS incidence over a 10-year period, we checked for increased prevalence in Southern Sardinia over a quinquennium. METHODS: ALS patients (El Escorial Criteria) recruited from the study area and followed at ALS Centre, University of Cagliari, were included. Prevalence was computed for January 1, 2015 and January 1, 2019 and was calculated for the overall ALS population as well as for tracheostomized and non-tracheostomized patients. RESULTS: We observed a non-significant trend for greater ALS prevalence in 2019 than in 2015 (18.31 per 100,000 vs. 15.26 per 100,000; rate ratio: 1.83, p = 0.01). By contrast, a significantly raising 2015 to 2019 ALS prevalence was observed in tracheostomized patients. No significant difference could be detected in non-tracheostomized. CONCLUSIONS: We provided the highest prevalence rate to date reported in the worldwide literature, and also showed a non-significant raising ALS prevalence in the Sardinian population over a quinquennium. The trend in raising ALS prevalence was likely due to extended survival due to invasive interventions.

Does epilepsy contribute to the clinical phenotype of C9orf72 mutation in fronto-temporal dementia?

C9orf72 mutation is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) worldwide. Recently, several reports of patients with FTD who carried the C9orf72 mutation and also manifested epilepsy have been published, since seizures occur in FTD at a higher rate than in the general population, the possible association between epilepsy and C9orf72 mutation remains to be clarified. In the attempt to understand whether epilepsy contributes to the phenotype of the C9orf72 mutation, we compared epilepsy occurrence in patients with FTD who carried the C9orf72 mutation and those who did not. In our sample of 84 patients with FTD, 7.1% of cases reported epilepsy, with no significant differences between subsamples of patients with FTD stratified according to the presence of the C9orf72 mutation or to family history of FTD/parkinsonism/motor neuron disease. Our findings did not support to the possibility that epilepsy represents a characteristic feature of the C9orf72 mutation, as suggested by recent case reports published in the English literature.

Incidence and spatial distribution of adult-onset primary malignant and other central nervous system tumors in Southern Sardinia, Italy.

PURPOSE: To study for the first time the incidence of adult-onset CNS tumors in Southern Sardinia, Italy. METHODS: Clinical records of patients > 18 years old who were diagnosed with primary CNS tumors during 2016-2019 in the study area were reviewed. Meningiomas, cranial/paraspinal nerve tumors, lymphomas, and pituitary tumors were excluded. Cases were classified according to the 2016 WHO classification of CNS tumors and to the morphology codes from the International Classification of Diseases-Oncology, third edition. Age-adjusted incidence rates were calculated by the direct method to the 2011-2020 European standard population. Kulldorff's spatial scan statistic was used to identify geographic clusters of patients who shared increased/decreased tendency to develop CNS tumors. RESULTS: CNS tumors were diagnosed in 234 incident patients, but histological diagnosis was available in 222/234 patients (95%) aged 64.3 ± 13.5 years at diagnosis. Crude incidence rate was 7.1 per 100,000 persons-year (95% CI, 6.2-8.1), 6.2 per 100,000 persons-year (95% CI, 5.4-7.0) when age-adjusted. CNS tumors were more frequent in men and after age 40. Glioblastoma accounted for 76% of the total (adjusted rate, 4.7 per 100,000 persons-year; 95% CI, 4.0-5.4). Spatial analysis revealed geographic variations of glioblastoma incidence within the study area. CONCLUSION: Although the distribution of tumor diagnoses in Sardinia reflects expected age and gender-related patterns in western populations, our findings would indicate a slightly higher incidence of glial tumors, glioblastoma in particular, in Sardinia than in other European countries. The identification of spatial clusters of high/low risk will serve as a resource for etiological research.

Reshaping cortical connectivity in traumatic spinal cord injury: a novel effect of hyperbaric oxygen therapy.

INTRODUCTION: Spinal cord injuries (SCIs) represent a severe neuro-traumatic occurrence and an excruciating social burden. Though the hyperbaric oxygen (HBO2) has been credited as a first line therapeutic resource for SCIs, its mechanism of action in the spine is only partially known, while the impingement upon other areas of the nervous system deserves additional investigation. In this study we deem to describe a novel effect of HBO2 in a subject affected by SCI who, along with the clinical improvement, showed a reshaped connectivity in cortical sensory-motor areas. CASE PRESENTATION: A 45 years male presenting severe sensory-motor symptoms following a spinal lesion partially involving the C1 segment was successfully treated with HBO2 cycles. After the dramatic improvement reflected by an excellent optimization of the single performances, it has been investigated whether this result would reveal not only an intrinsic effect upon the spinal cord, but also a better connectivity strength in sensory-motor cortical regions. The results obtained by implementing EEG recordings with EEGLAB auto regressive vector plugins indeed suggest a substantial reshaping of cortico-cortical connectivity after HBO2. DISCUSSION: These results show a correlation between positive clinical evolution and a new modulation of cortical connectivity. Though further clinical investigations would clarify as to whether HBO2 might be directly or epiphenomenally involved in this aspect of the network architecture, our report suggests that a comparison between clinical results and the study of brain connectivity represent a holistic approach in investigating the physiopathology of SCIs and in monitoring the treatment.

Geographic differences in the incidence of Huntington's disease in Sardinia, Italy.

BACKGROUND: The frequency of Huntington's disease (HD) may vary considerably, with higher estimates in non-Asian populations. We have recently examined the prevalence of HD in the southern part of Sardinia, a large Italian Mediterranean island that is considered a genetic isolate. We observed regional microgeographic differences in the prevalence of HD across the study area similar to those recently reported in other studies conducted in European countries. To explore the basis for this variability, we undertook a study of the incidence of HD in Sardinia over a 10-year period, 2009 to 2018. METHODS: Our research was conducted in the 5 administrative areas of Sardinia island. Case patients were ascertained through multiple sources in Sardinia and Italy. RESULTS: During the incidence period 53 individuals were diagnosed with clinically manifested HD. The average annual incidence rate 2009-2018 was 2.92 per 106 persons-year (95% CI, 2.2 to 3.9). The highest incidence rate was observed in South Sardinia (6.3; 95% CI, 4.2-9.5). This rate was significantly higher (p<0.01) than the rates from Cagliari, Oristano, and Sassari provinces but did not significantly differ (p = 0.38) from the Nuoro rate. CONCLUSIONS: The overall incidence of HD in Sardinia is close to the correspondent estimates in Mediterranean countries. Our findings highlight also the possibility of local microgeographic variations in the epidemiology of HD that might reflect several factors, including a possible founder effect in the rural areas of South Sardinia and Nuoro.

Development of a Clinical Rating Scale for the Severity of Apraxia of Eyelid Opening, Either Isolated or Associated with Blepharospasm.

BACKGROUND: Apraxia of eyelid opening is a movement disorder characterized by an inability to raise the eyelids without any overt contractions of the orbicularis oculi muscle. There is currently no clinical scale to rate the severity of this condition. OBJECTIVES: To develop and validate a novel scale that considers phenomenological aspects relevant to the severity of the condition. METHODS: The study sample included 20 patients with apraxia of eyelid opening, either isolated (9 patients) or associated with blepharospasm (11 patients). To validate the scale, selected features were checked for reliability, reliable items were combined to generate the scale, and clinimetric properties were evaluated. RESULTS: The novel severity scale yielded acceptable reliability, scaling assumptions, internal consistency, and sensitivity to change; a lack of floor and ceiling effects; and no correlation with the blepharospasm severity rating scale. CONCLUSIONS: We propose a severity scale that considers the most relevant apraxia of eyelid opening motor abnormalities based on objective criteria. This scale can be reliably administered by general neurologists after a brief training.

Prevalence of Huntington's disease in Southern Sardinia, Italy.

BACKGROUND: The frequency of Huntington's disease (HD) may vary considerably, with higher estimates in non Asian populations. In Italy, two recent studies performed in Ferrara county and Molise provided different prevalence estimates, varying from 4.2 × 105 to 10.8 × 105. Here we present a study performed in the Southern part of Sardinia, a large Italian mediterranean island that is considered a genetic isolate. METHODS: The study area included the two neighbouring counties of South Sardinia and Cagliari with 353,830 and 431,955 inhabitants respectively on December 31st, 2017 (prevalence date). Case-patients were ascertained through multiple sources in Sardinia and Italy. RESULTS: We identified 54 individuals with HD, of whom 47 were alive on prevalence date. The resulting prevalence rate was 5.98 × 105 in the overall study area, however with marked variations between South Sardinia and Cagliari (9.6 × 105 vs. 3.0 × 105, p = 0.02). In the two study areas, we found similar CAG repeat length in normal alleles (17.5 ± 2.1 vs. 17.7 ± 2.2, p = 0.5). CONCLUSIONS: The overall prevalence of HD in Sardinia is close to the correspondent estimates in Europeans. Our findings also highlighted the possibility of local microgeographic variations in the epidemiology of HD.

Cerebellar Syndrome Associated with Thyroid Disorders.

Thyroid disorders, including hypothyroidism, hyperthyroidism and Hashimoto encephalopathy, are considered the most common cause of cerebellar dysfunction due to hormonal imbalance. Typically, cerebellar impairment occurs in the course of hypothyroidism and Hashimoto encephalopathy. Information about demographic, clinical and laboratory features of cerebellar disease associated with thyroid disorders is poor. Our review of the literature (1965 to 2018) identified 28 cases associated with hypothyroidism and 37 cases associated with Hashimoto encephalitis. Both patients with hypothyroidism and Hashimoto encephalopathy presented with signs of ataxia that were similarly distributed in the two groups and were mostly predictive of vermis involvement and frequent impairment of cerebellar hemispheres. Additional neurological signs, like dystonia, psychiatric symptoms, ocular disturbances and myoclonus, could be found in the Hashimoto encephalopathy group alone. When present, atrophy of vermis and often of both cerebellar hemispheres was the main imaging abnormality in both hypothyroidism and Hashimoto encephalopathy. Anti-thyroid antibodies could be detected in three quarters of patients with hypothyroidism and in all patients with Hashimoto encephalopathy. In the patients with hypothyroidism, thyroid replacement therapy yielded complete or partial remission of ataxia. In the Hashimoto encephalopathy group, immunosuppressive treatment provided complete remission of ataxia in about 60% of patients, partial remission in the remaining cases. Owing to the treatable nature of the condition and the high prevalence of thyroid disease among general population, cerebellar syndrome associated with thyroid disorders should be considered an important clinical entity. Information from this review will hopefully stimulate and strengthen awareness of thyroid-associated ataxia among clinicians.

Status epilepticus in Hashimoto's encephalopathy.

Hashimoto's encephalopathy is a non-infectious, probably autoimmune encephalitis, characterized by varied signs coupled with elevated levels of anti-thyroid antibodies and, often, good response to corticosteroid therapy. Seizures, namely focal and generalized tonic-clonic seizures, myoclonus, and status epilepticus, are frequent manifestations of Hashimoto's encephalopathy. Typically, seizures in these patients respond poorly to anti-epileptic drugs. Although cases of Hashimoto's encephalopathy with status epilepticus have been reported in literature, they vary in demographic, clinical, and treatment characteristics. We could not identify any systematic review summarizing the evidence in regard to factors predicting the occurrence of status epilepticus in Hashimoto's encephalopathy and the responsiveness of status epilepticus to anti-epileptic drugs, steroids and other immunomodulatory medication. Therefore, we performed an extensive review of the literature to identify and compare Hashimoto's encephalopathy patients presenting with and without status epilepticus. In 31 patients with status epilepticus and 104 patients without status epilepticus, thyroid status, anti-thyroid antibodies, cerebrospinal fluid analysis, brain MRI/CT/SPECT scan did not predict occurrence of status epilepticus of variable phenomenology. Status epilepticus did not respond to anti-epileptic drugs but completely remitted under steroid treatment, alone or in combination with other immunomodulatory medication, in about three quarter of patients. Generalized convulsive status epilepticus might be a factor negatively influencing outcome.