Kleine-Levin syndrome: report of a case with marked dysautonomic features.

Kleine-Levin syndrome is a rare neurologic disorder of unknown etiopathogenesis, characterized by abrupt onset and remission of attacks of hypersomnia and cognitive dysfunctions. Psychiatric symptoms are frequently present, ranging from disinhibited sexual behavior and eating disorders to hallucinations, anxiety, mood alterations, and derealization. A vast range of attack-related dysautonomic signs and symptoms are reported but remain poorly described. We describe a patient with Kleine-Levin syndrome with sleep attacks dominated by marked dysautonomic features. We briefly review similar clinical cases and suggest that the hypothalamus may play a central role in the genesis of autonomic dysfunction in Kleine-Levin syndrome. CITATION: Fiamingo G, Esposto R, Dal Fabbro B, Terzaghi M. Kleine-Levin syndrome: report of a case with marked dysautonomic features. J Clin Sleep Med. 2022;18(9):2313-2316.

Clinical-Genetic Features Influencing Disability in Spastic Paraplegia Type 4: A Cross-sectional Study by the Italian DAISY Network.

Background and Objectives: Hereditary spastic paraplegias (HSPs) are a group of inherited rare neurologic disorders characterized by length-dependent degeneration of the corticospinal tracts and dorsal columns, whose prominent clinical feature is represented by spastic gait. Spastic paraplegia type 4 (SPG4, SPAST-HSP) is the most common form. We present both clinical and molecular findings of a large cohort of patients, with the aim of (1) defining the clinical spectrum of SPAST-HSP in Italy; (2) describing their molecular features; and (3) assessing genotype-phenotype correlations to identify features associated with worse disability. Methods: A cross-sectional retrospective study with molecular and clinical data collected in an anonymized database was performed. Results: A total of 723 Italian patients with SPAST-HSP (58% men) from 316 families, with a median age at onset of 35 years, were included. Penetrance was 97.8%, with men showing higher Spastic Paraplegia Rating Scale (SPRS) scores (19.67 ± 12.58 vs 16.15 ± 12.61, p = 0.009). In 26.6% of patients with SPAST-HSP, we observed a complicated phenotype, mainly including intellectual disability (8%), polyneuropathy (6.7%), and cognitive decline (6.5%). Late-onset cases seemed to progress more rapidly, and patients with a longer disease course displayed a more severe neurologic disability, with higher SPATAX (3.61 ± 1.46 vs 2.71 ± 1.20, p < 0.001) and SPRS scores (22.63 ± 11.81 vs 12.40 ± 8.83, p < 0.001). Overall, 186 different variants in the SPAST gene were recorded, of which 48 were novel. Patients with SPAST-HSP harboring missense variants displayed intellectual disability (14.5% vs 4.4%, p < 0.001) more frequently, whereas patients with truncating variants presented more commonly cognitive decline (9.7% vs 2.6%, p = 0.001), cerebral atrophy (11.2% vs 3.4%, p = 0.003), lower limb spasticity (61.5% vs 44.5%), urinary symptoms (50.0% vs 31.3%, p < 0.001), and sensorimotor polyneuropathy (11.1% vs 1.1%, p < 0.001). Increasing disease duration (DD) and abnormal motor evoked potentials (MEPs) were also associated with increased likelihood of worse disability (SPATAX score>3). Discussion: The SPAST-HSP phenotypic spectrum in Italian patients confirms a predominantly pure form of HSP with mild-to-moderate disability in 75% of cases, and slight prevalence of men, who appeared more severely affected. Early-onset cases with intellectual disability were more frequent among patients carrying missense SPAST variants, whereas patients with truncating variants showed a more complicated disease. Both longer DD and altered MEPs are associated with worse disability.

Correlation of Frontal Atrophy and CSF Tau Levels With Neuropsychiatric Symptoms in Patients With Cognitive Impairment: A Memory Clinic Experience.

Background: Behavioral and psychological symptoms of dementia (BPSD) are a distressful condition. We aimed to investigate the BPSD distribution in subjects with cognitive impairment, and the potential correlations between BPSD and neurodegeneration in terms of cerebrospinal fluid (CSF) tau and brain atrophy. Methods: One-hundred patients with mild cognitive impairment (MCI) or dementia (Alzheimer's disease, AD; Lewy-body disease, LBD; frontotemporal dementia, FTD; vascular dementia, VD) underwent a complete diagnostic workup, including 3T-MRI and/or CT and CSF. Cortical atrophy was assessed with medial temporal atrophy (MTA), posterior atrophy (PA), and global cortical atrophy-frontal lobe (GCA-F) scales. BPSD were rated using the Neuropsychiatric Inventory (NPI), and BPSD clusters were defined according to the European Alzheimer Disease Consortium. Results: Delusions, hallucinations, and psychosis cluster were differently distributed among the diagnostic groups (p < 0.05, p < 0.001, and p < 0.05), with LBD patients showing higher scores for hallucinations (vs. MCI, p < 0.001, and AD, p < 0.05) and psychosis cluster (vs. MCI, p < 0.05). In primary dementias, we found a negative correlation between NPI total score and tau levels (p = 0.08), confirmed by beta regression (p < 0.01), while a positive non-significant relationship was observed in MCI. Higher GCA-F scores were associated with delusions and apathy (p < 0.05, on both hemispheres) and hallucinations (left: p < 0.01, right: p < 0.05). GCA-F scores were positively correlated with psychosis cluster (right: p < 0.05), and agitation/aggression (left: p < 0.05). Conversely, nighttime disturbances were positively correlated with both GCA-F and MTA scores (left: p < 0.01; right: p < 0.05). Conclusion: Our results suggest that psychotic symptoms are significantly more represented in LBD patients and that CSF tau and frontal atrophy are associated with the occurrence and severity of BPSD in clinical practice. Longitudinal studies are however required to ascertain their actual predictive value.