The vascular locked-in and locked-in-plus syndrome: A retrospective case series.

The locked-in syndrome (LiS) is defined as the loss of most voluntary muscle movements with preserved cognitive abilities due to a ventral pontine lesion. However, some patients may also have severe impairment of consciousness [locked-in plus syndrome (LiPS)]. Here we aimed to explore structural differences between LiS and LiPS patients of vascular aetiology, focusing on lesion patterns and locations to better delineate the clinical spectrum of LiS and LiPS. In this retrospective case series study, we report nine patients (two women), ages 29-74 years (median 50) with LiS and LiPS who were diagnosed between 2007 and 2021. Clinical parameters, MRI findings including the lesioned structures, and a shape feature calculation are presented for every patient. The lesioned structures were determined by a senior neuroradiologist. Two of nine patients had fully retained consciousness (LiS) and seven showed various degrees of impaired consciousness (LiPS). Lesions of LiS patients are round and confined to the pons, whereas lesions of LiPS patients are more elongated and reach neighbouring areas such as the mesencephalon, thalamus or ascending reticular activating system. Lesions involving the mesencephalon and the thalamus are strong indicators of LiPS, whereas for lesions restricted to the pons, the dorsal extension and the associated damage to the ascending reticular activating system are crucial to differentiate LiS from LiPS. Recognizing LiPS using clinical and radiological findings is important as these patients may need different therapies and care and, most importantly, should not be mistaken as unresponsive wakefulness syndrome.

Vitamin D deficiency promoting non-24 h sleep-wake disorder: a case report.

We report a case of an emmetropic woman with excessive daytime sleepiness in alternation with insomnia consistent with the diagnosis criteria of a non-24 h sleep-wake disorder. After being refractory to the usual non-pharmacologic and pharmacologic treatment, we detected a deficiency of vitamin B12, vitamin D3, and folic acid. Substitution of these treatments led to a return of a 24 h sleep-wake rhythm though this remained independent from the external light-dark cycle. The question arises whether the vitamin D deficiency could be regarded as an epiphenomenon or whether there is an up-to-date unknown connection to the inner zeitgeber.

Life-threatening vitamin D intoxication due to intake of ultra-high doses in multiple sclerosis: A note of caution.

Knowledge about complications of chronic ultra-high dose vitamin D supplementation is limited. We report a patient with primary progressive multiple sclerosis (MS) who presented with generalized weakness caused by hypercalcemia after uncontrolled intake of more than 50,000 IU of cholecalciferol per day over several months. Various treatment strategies were required to achieve normocalcemia. However, renal function improved only partly and further progression of MS was observed. We conclude that patients need to be informed about the risks of uncontrolled vitamin D intake and neurologists need to be alert of biochemical alterations and symptoms of vitamin D toxicity.

Dopamine differently modulates central cholinergic circuits in patients with Alzheimer disease and CADASIL.

Short-latency afferent inhibition (SAI) technique gives the opportunity to non-invasively test an inhibitory circuit in the human cerebral motor cortex that depends mainly on central cholinergic activity. Important SAI abnormalities have been reported in both patients with Alzheimer disease (AD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a model of "pure" vascular dementia (VD). Interestingly, a normalization of SAI was observed in AD after levo-dopa (L-dopa) administration. We aimed to determine whether the pharmacological manipulation of the dopaminergic system can also interfere with SAI test in CADASIL patients, compared with AD patients and healthy controls. SAI was found to be significantly reduced in both patient groups. L-Dopa significantly increased SAI in the AD patients, while it failed to restore SAI abnormality in CADASIL patients. Therefore, L-dopa-mediated changes on SAI in AD patients seem to be a specific effect. The present study supports the notion that relationship between acetylcholine and dopamine systems may be specifically abnormal in AD. L-Dopa challenge may thus be able to differentiate the patients with AD or a mixed form of dementia from those with "pure" VD.

Biomarkers of inflammation and endothelial dysfunction in stroke with and without sleep apnea.

OBJECTIVE: Although sleep apnea (SA) is a risk factor for ischemic stroke and an important prognostic factor in affected patients, the exact pathophysiological link between SA and stroke is unknown. We investigated whether the plasma concentration of biomarkers of inflammation and endothelial dysfunction, including soluble tumor necrosis factor receptor-1 and -2 (sTNF-R1 and sTNF-R2), tumor necrosis factor-ß (TNF-ß), soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) are increased in patients with acute stroke and SA compared with stroke patients without SA. DESIGN/METHODS: In total, 76 patients with ischemic stroke admitted to the stroke unit were included in this study. Plasma concentrations of biomarkers were determined after CT scans on admission. All patients received cardiorespiratory polygraphy within the first 72 h after admission. In all patients, demographic data, National Institutes of Health Stroke Scale scores and cerebrovascular risk factors were assessed. RESULTS: An apnea-hypopnea index (AHI) ≥10/h was found in 37 of our patients (48.7%). In these patients with SA, sTNF-R1 and sTNF-R2 levels were significantly higher than in patients with an AHI lower than 10/h. TNF-ß, however, showed no significant difference between both groups, just like the soluble intercellular and vascular cell adhesion molecules sICAM-1 and sVCAM-1. CONCLUSIONS/RELEVANCE: SA is associated with raised levels of sTNF-R1 and sTNF-R2 in patients with acute ischemic stroke. Taking into account the established impact of these two markers on the causation and course of cerebrovascular disease, these proteins may be part of the pathophysiological pathway linking SA to stroke.