Anti-IGLON5 disease: A new case without neuropathologic evidence of brainstem tauopathy.

OBJECTIVE: To describe the neuropathologic features and the molecular data of phosphorylated tau (pTau) in a new case of anti-IgLON5 disease. METHODS: Review of clinical data, postmortem neuropathologic examination. Biochemical analyses of pTau were performed in brain samples from the present case and from a previously described patient with anti-IgLON5 with the characteristic brainstem tauopathy. RESULTS: The patient was a 71-year-old man with a clinical syndrome consisting of sleep disturbance and bulbar symptoms. IgLON5 antibodies of predominant IgG4 subtype were detected in serum and CSF. He carried the HLA DRB1*10:01-DQB1*05:01 haplotype. Despite treatment with IV immunoglobulins, he unexpectedly died during sleep 2 years after disease onset. Histology showed neurofibrillary pathology and ß-amyloid deposits consistent with Alzheimer disease (AD) of intermediate severity. pTau deposits were absent in the brainstem. There were few perivascular CD8+ T-cell infiltrates in the posterior hypothalamus, amygdala, and brainstem with microglial activation. The pTau immunoblot showed a pattern of bands consistent with AD, which was different from that observed in the patient with anti-IgLON5 with brainstem tauopathy who presented a differential band around 56 KDa. CONCLUSION: The absence of pTau deposits in the brainstem of the present patient suggests that the tauopathy of patients with anti-IgLON5 disease may be a late, secondary event. The anti-IgLON5 brainstem tauopathy has a specific molecular signature different from primary tauopathies. pTau deposits restricted to the hippocampus/limbic regions of patients with anti-IgLON5 may represent an age-related comorbidity.

Hereditary Spastic Paraplegia and Intellectual Disability: Clinicogenetic Lessons From a Family Suggesting a Dual Genetics Diagnosis.

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of genetic disorders with spastic paraparesis as the main clinical feature. Complex forms may co-occur with other motor, sensory, and cognitive impairment. A growing number of loci and genes are being identified, but still more than 50% of the patients remain without molecular diagnosis. We present a Spanish family with autosomal dominant HSP and intellectual disability (ID) in which we found a possible dual genetic diagnosis with incomplete penetrance and variable expressivity in the parents and three siblings: a heterozygous duplication of 15q11.2-q13.1 found by array CGH and a novel missense heterozygous change in REEP1 [c.73A>G; p.(Lys25Glu)] found by whole exome sequencing (WES). Following the standard genetic diagnosis approach in ID, array CGH analysis was first performed in both brothers affected by spastic paraparesis and ID from school age, and a heterozygous duplication of 15q11.2-q13.1 was found. Subsequently, the duplication was also found in the healthy mother and in the sister, who presented attention deficit/hyperactivity disorder (ADHD) symptoms from school age and pes cavus with mild pyramidal signs at 22 years of age. Methylation analysis revealed that the three siblings carried the duplication unmethylated in the maternal allele, whereas their mother harbored it methylated in her paternal allele. Functional studies revealed an overexpression of UBE3A and ATP10A in the three siblings, and the slightest cognitive phenotype of the sister seems to be related to a lower expression of ATP10A. Later, searching for the cause of HSP, WES was performed revealing the missense heterozygous variant in REEP1 in all three siblings and the father, who presented subtle pyramidal signs in the lower limbs as well as the sister. Our findings reinforce the association of maternally derived UBE3A overexpression with neurodevelopmental disorders and support that a spectrum of clinical severity is present within families. They also reveal that a dual genetic diagnosis is possible in patients with presumed complex forms of HSP and cognitive impairment.

Ictal Video-Electroencephalography Findings in Bathing Seizures: Two New Cases and Review of the Literature.

INTRODUCTION: Reflex bathing seizures are described during the course of bathing in water near body temperature. These seizures differ from other epilepsies characterized by bathing-induced seizures such as hot water epilepsy, but there are few well-described patients and only some of these have been documented by ictal video-electroencephalography. METHODS: Our objective was to characterize the clinical presentation of bathing-induced seizures demonstrated by ictal video-electroencephalographic recordings with water temperature below 38°C. We described two previously unreported infants and reviewed additional cases in the literature that fulfilled those criteria. RESULTS: Eighteen infants were indentified. They were predominantly male (72%), and the mean age of seizure onset was 15 months (one to 36 months). The most frequent seizure triggers included pouring water over the face and immersion. Seizures were of focal onset with loss of awareness and prominent autonomic symptoms. Ictal video-electroencephalography revealed delta-theta high-amplitude focal waves involving temporal and adjacent regions, with a rapid spread to the ipsilateral hemisphere or generalization. Avoiding known triggers usually controlled the seizures, but carbamazepine, valproate, and levetiracetam were also helpful. Neuroimaging was normal in all cases, and neurodevelopment was unaffected. DISCUSSION: Bathing seizures predominate in boys with an early onset and a benign self-limited course. The use of ictal video-electroencephalographic recordings in these cases leads to diagnosis and reveals individual differences in triggers.

Trastornos del movimiento y de la conducta durante el sueño en el adulto / Sleep-related movement and behavioural disorders in adults

Los trastornos del movimiento y de la conducta durante el sueño pueden tener un impacto en la calidad del sueño del paciente y dar lugar a síntomas diurnos. En estos grupos de enfermedades se incluyen entidades como el síndrome de piernas inquietas, los movimientos periódicos de las piernas y las parasomnias del sueño de movimientos oculares rápidos (REM) y no REM. El conocimiento de sus características clínicas y nociones sobre su manejo es de gran importancia para el neurólogo y especialista en sueño por su frecuencia e impacto en la calidad del sujeto. Con frecuencia, estos pacientes son referidos a dichos especialistas, y es relevante conocer que ciertos trastornos del sueño pueden asociarse a otras enfermedades neurológicas

Sleep-related movement and behaviour disorders may have an impact on sleep quality and lead to daytime symptoms. These groups of conditions include diseases such as restless legs syndrome, periodic leg movements, and REM and NREM parasomnias. The knowledge of their clinical features and management is of utmost importance for the neurologist and sleep specialist. Frequently, these patients are referred to such specialists and it is relevant to know that certain sleep disorders may be associated with other neurological conditions