Leek et al. demonstrate that patients with a new diagnosis of focal epilepsy show evidence of atrophy of the thalamus and hippocampus. These findings challenge the idea that brain atrophy in focal epilepsy exclusively results from the chronicity of the disorder in medically refractory patients.

A 35-year-old man with a family history of early-onset dementia presented with personality changes, behavioral disturbances and forgetfulness. Based on the mild cerebral atrophy on MRI and hypometabolism in bilateral temporal and parietal lobes on PET studies, the diagnosis was initially considered as familial Alzheimer’s disease. Whole-exome sequencing revealed the presence of a heterozygous G131V variant in the PRNP gene, establishing a diagnosis of familial prion disease.

Cognitive frailty is a combination of physical frailty and cognitive impairment. Cognitive frailty is associated with falls and increases the risk of future falls.

Protein tyrosine phosphatase receptor type Q (PTPRQ) extracted from CSF of patients with probable idiopathic normal pressure hydrocephalus (iNPH) by proteome analysis was evaluated as potential biomarker for this condition. Its level from two cohorts - Japanese and Finnish was compared with normal controls and non-iNPH patients. The levels were significantly lower than non-iNPH patients, but higher than normal controls. It is highly possible that the elevated PTPRQ levels in CSF are related to ependymal dysfunction from ventricular expansion. CSF PTPRQ levels indicated the validity of this assay for auxiliary diagnosis of adult chronic hydrocephalus.

Preexisting moderate-to-severe white matter hyperintensities negatively affect the restoration of cognitive function after recent small subcortical infarct, suggesting limited functional reserve in patients with preexisting small vessel disease.

More than 1.4 million people 65 years of age or older were followed in Danish registry data. Findings show that people with dementia have a substantially increased mortality rate (sixfold) following an infection that goes beyond the mortality rates observed in people with dementia alone, infections alone, or the sum of these rates. Increased mortality was observed following all types of infections (highest for sepsis and lowest for ear infections) and was both short term (30 days) and long term (10 years).

Amyotrophic lateral sclerosis (ALS) risk increases with age. A log-incidence versus log-age curve suggests that five to six factors are involved in disease onset. The factors remain unidentified, except that fewer steps are predicted for those with an ALS-causing mutation. Consistent with previous research, we find a linear ALS-onset relationship in the Danish population. This did not differ when considering ALS cases with a prior psychiatric diagnosis. Assessment of a prior cardiovascular disease (CVD) diagnosis in ALS in a CVD population and a meta-analysis of males versus females demonstrated fewer steps to disease. The underlying contributing mechanisms for CVD/sex and ALS are unknown and probably complex.

Pioglitazone and statins may lower the indidence of Parkinsion disease independently and synergistically in patients with diabetes mellitus.

Newly diagnosed Parkinson’s disease patients who develop minor hallucinations during the first 5 years of disease exhibit more extensive GMV loss at baseline and an increased rate of atrophy in the first years after diagnosis. These patients also showed an increased prevalence of subjective cognitive decline. Longer follow-up analyses would be needed to further define if these findings could reflect a higher risk of future cognitive deterioration.

This resting-state functional magnetic resonance imaging study applied graph methods, which revealed dopaminergic-related alterations in a broad array of brain networks in restless legs syndrome (RLS) patients. In particular, lower cerebello-parietal connectivity was present in untreated RLS, but not in medicated patients. RLS patients treated solely with dopaminergic medication presented with higher thalamo-frontal connectivity compared to untreated patients.

We studied the clinical features and the genetic background that underline impulse control disorders (ICDs) in 532 Parkinsons’s disease (PD) patients. Treatment with dopamine agonists increased the risk of ICDs and it was dose dependent (P < 0.05). The DOPA decarboxylase gene (DDC) variant, rs1451375, might modulate the risk of ICDs in PD. The predictability of experiencing ICDs increased an 11% by adding genetic factors to clinical features. It is therefore important to assess the patient’s genetic background to identify individuals at risk for ICDs.

We examined the contribution of clinical care on sex differences and health-related quality of life (HRQoL) after stroke. First-ever strokes registered in the Australian Stroke Clinical Registry (2010–2014) with HRQoL assessed between 90 and 180 days after onset using the EQ-5D-3L instrument) were included. Women with stroke had poorer HRQoL than men in unadjusted analysis, and the difference was explained by age and stroke severity, but not clinical care.

In this multicentre observational study including 74 patients with isolated internal carotid artery occlusion (i.e. without associated intracranial occlusion) with minor baseline symptoms (NIHSS score <6) and treated with IV-thrombolysis, Early Neurological Deterioration (END) within 24hrs occurred in 30% of patients and was strongly associated with poor 3-month outcome. The predominant END mechanism was thrombo-embolic, as evidenced by a new intracranial occlusion in 3 out of 4 END cases. Supra-bulbar carotid occlusion site –largely a function of underlying stroke etiology– was the only predictor of END, which may point to a different response of the thrombus to IV-thrombolysis.

In this study, we aimed to assess the prognostic implications and hospital costs of initial admission of patients with low-grade aneurysmal subarachnoid hemorrhage (aSAH) to stroke units (SUs) compared to initial admission to intensive care units (ICUs). For that purpose, we reviewed prospectively registered data from all consecutive aSAH patients with a World Federation of Neurosurgery Societies grade <3 admitted to our Comprehensive Stroke Centre between April 2013 and September 2018. We found that initial admission to a SU resulted in similar rates of in-hospital complications and clinical outcome metrics compared to initial admission to an ICU.

Graphical Table of Contents Among 896 patients (559 men, median age of 70 years) with diagnosis of a tissue-based transient ischemic attack (TIA), 59 (6.6%) were unaware of their symptoms but had their symptoms witnessed by bystanders. The cumulative incidence rate of occurrence of ischemic stroke after 1 year from TIA was higher in patients without self-awareness than those with self-awareness (16.3% vs. 6.9%, log-rank; P = 0.010).

The biological mechanisms underlying the association between migraine and ischemic stroke remain unclear. Growing evidence suggests that cerebral micro embolization of cardiac origin might trigger migraine attack in the context of increased cortical hyperexcitability, thereby contributing to the stroke risk in migraineurs. The results of this study indicate that the relation between cardio embolism and migraine is unlikely to be explained by atrial fibrillation (AF), but rather, by interatrial right-to-left shunt (patent foramen ovale, PFO). This seems especially true for the subtype migraine with aura, for younger subjects who have a more favorable vascular risk factor profile, and for women.

Exploring safety of head down 15° (HDT15°) application in the acute phase of intracerebral hemorrhage is highly relevant for its translation into a collateral therapeutic for prehospital treatment of acute ischemic stroke. Application of head down tilt 15° for 1 h in a rat model of large supratentorial intracerebral hemorrhage does not worsen early outcome compared to flat position in terms of hematoma volume, hematoma growth, mass effect, mortality, and functional deficit at 24 h. Intracranial pressure was increased by a few millimeters of mercury (+2.91 ± 1.76 mmHg) after HDT15° application.

In a post hoc analysis of the WAKE-UP trial, polypharmacy, independently of pre-existing comorbidities, was associated with worse functional outcome after stroke. Notably, polypharmacy did not modulate the therapeutic effect of intravenous thrombolysis. Based on these results, it is concluded that treatment with alteplase is safe and efficient in patients with polypharmacy, and polypharmacy should not be a reason to exclude these patients from treatment.

B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are well-known surrogates of atrial fibrillation (AF) detection but studies usually present data on either BNP or NT-proBNP. In our study, both BNP and NT-proBNP were increased in cryptogenic stroke patients with AF detection. Interestingly, BNP outperforms NT-proBNP, especially in terms of specificity.

Mean costs associated with informal care provided by the main informal caregivers to patients with IS (base case analysis and sensitivity analyses 2, 3, and 4). Informal care time was valued using the Proxy Good Method in the base case analysis and using the Opportunity Cost Method in sensitivity analysis 2. In sensitivity analysis 3, care time estimation was replaced using the iCARE tool for all patients. In sensitivity analysis 4, care time estimation was replaced using the iCARE tool only for patients with missing data. Bars represent standard errors.

The age-, sex-, and race-adjusted prevalence of hypertension is 25% higher in multiple sclerosis (MS) patients than non-MS patients. This elevated age- and sex-adjusted burden of hypertension is irrespective of being Black (23% higher) or White (25%) American.

A cohort of 7964 relapsing-remitting multiple sclerosis patients (RRMS) followed for 2 or more years, with Expanded Disability Status Scale (EDSS) scores recorded every 6 months, was selected from the Italian Multiple Sclerosis Register to compare the cumulative probability of 6-month confirmed disability-worsening events using a fixed baseline or a roving EDSS reference. Using a roving EDSS reference method, the 6- and 10-year cumulative probabilities of worsening events unrelated to relapses almost doubled. In this real-world setting, in RRMS patients, roving EDSS reference scores appear to be more sensitive for detecting confirmed disability-worsening events unrelated to relapse.

Epstein–Barr virus infection after adolescence and age independent human herpesvirus 6A infection are risk factors for multiple sclerosis.

Phenytoin treatment in acute optic neuritis demonstrates a reduction in serum NfH levels at 3 months, but not in NfL.

This is the first study reporting non-HLA susceptibility genes for anti-NMDAR encephalitis. BANK1, IRF7 and TBX21 polymorphisms were associated with anti-NMDAR encephalitis. IRF7 rs1131665 was associated with tumor status in anti-NMDAR encephalitis.

Percentages of regularly followed patients and newcomers.

The authors describe detailed clinical, genetic and radiological aspects of Brazilian patients with adult-onset spinal muscular atrophy (SMA type 4), scarcely described previously in the literature. New important muscle imaging and genetic findings are also presented and bring important contributions to clinical practice.

In most reported CIDP series, there is a consistent proportion of patients who have the clinical features compatible with a diagnosis of CIDP but who do not fulfill the EFNS/PNS electrodiagnostic criteria and, therefore, might be denied the access to effective therapy. In our study, patients with a clinical diagnosis of CIDP had similar clinical findings, frequency of abnormal supportive criteria and response to therapy compared to patients fulfilling EFNS/PNS criteria. The presence of abnormal supportive criteria may help supporting the diagnosis of CIDP in patients with a medical history and clinical signs compatible with this diagnosis but non-diagnostic nerve conduction studies.

Measurements of the corneal whorl-like nerve plexus by using corneal confocal microscopy (CCM) is a sensitive biomarker to detect small-fiber neuropathy of transthyretin familial amyloid polyneuropathy (TTR-FAP) patients in an early stage. The whorl-like pattern of the corneal nerve also provides a static landmark to monitor disease progression.

This retrospective study of 34 patients with generalized MG showed a successful transition from IVIG to SCIG therapy. Chronic IVIG for about 20 months, followed by transition to SCIG therapy for another 20 months was associated with improved MG status and reduced immunosuppressive therapy requirements.

Rhabdomyolysis events are provoked by exposure to external triggers, possibly in combination with an increased genetic susceptibility. Anoxia was the most frequently reported external trigger (40%). A subset of 193 patients (14.8%) were clinically suspected of an underlying genetic disorder. A total of 22 genes with pathogenic variants were identified, of which 11 have been previously associated with rhabdomyolysis (ACADVL, ANO5, CPT2, DMD, DYSF, FKRP, HADHA, PGM1, LPIN1, PYGM, RYR1). Eleven genes are probably implicated in increased susceptibility (including AGL, CAPN3, CNBP, DMPK, MAGT1, ACADM, SCN4A, SGCA, SGCG, SMPD1, TANGO2).

This large multicentric Parisian series delineates the clinical spectrum of patients with sarcoglycanopathies. Age at disease onset and absence of sarcoglycan expression on muscle biopsy are predictors of severity of disease and loss of ambulation, and should be taken into account in future clinical trials.

The presence of microbleeds/superficial siderosis in patients with logopenic progressive aphasia is a strong indicator of underlying moderate to severe cerebral amyloid angiopathy. Biological mechanisms underlying the topographic distribution of microbleeds remain unclear.

The administration of nusinersen in spinal muscular atrophy (SMA) patients with complex spines is challenging. This study provides Class IV evidence that the ultrasound-guided lumbar puncture, following an interlaminar parasagittal approach, is safe and effective and could be considered as the first approach, especially in younger SMA patients.

As part of the European Brain Council-led Value of Treatment project, this study aimed to investigate the cost-effectiveness of delivering timely and adequate normal-pressure hydrocephalus (NPH) treatment in Germany. We showed that appropriate treatment, using shunt surgery for idiopathic NPH, is cost-effective. Shunt surgery resulted in a gain in lives and quality-adjusted life-years (QALYs), along with an incremental cost per patient of €10 202/QALY per 5 years (up to €35 000 within 15 years after surgery). This represents a substantial gain for elderly persons and a greater gain and lower cost/QALY than for many comparable standard interventions.

As part of the European Brain Council (EBC)-led Value-of-Treatment (VoT) Project, this study aimed at capturing the socio-economic impact of RLS related to the inadequate diagnosis and treatment across different European healthcare settings. RLS proved to be a significant personal and social burden, when including epidemiological data and high prevalence of RLS and its need for treatment. By looking at the savings emerging from the provision of optimal care management, the authors foresee substantial economic savings with the achievement of adequate diagnosis and treatment of RLS.

As part of the European Brain Council (EBC)-led Value of Treatment Project, this study aimed to capture the economic benefit of a timely, adequate, and adherence to PD treatment. The economic analyses confirmed the benefits of timely, adequate, and adherence to PD treatment. It will not only improve care of the patients but is also cost-effective (when addressing gap 2: providing adequate treatment for advanced PD) and cost-saving (when addressing gaps 1 and 3: providing early/timely treatment and improving the rates of adherence to optimal care) across healthcare systems.

To reduce the >30 billion euros annual cost of stroke to the EU, we identified key unmet needs in the stroke patient pathway including:

• inadequate treatment of atrial fibrillation
• access to neurorehabilitation
• implementation of Comprehensive Stroke Services.

In a Markov model, full implementation of stroke services was associated with a 9.8% reduction in death and dependency, with an incremental cost effectiveness ratio of £5,228, robust to possible variations in cost and effectiveness. Meeting these needs has the potential to significantly reduce death and disability due to stroke in the EU, and is highly cost-effective.

A 29-year-old male patient presented with a 1-year history of progressive slowing of movements with stiffness, dysarthria, and dysphagia. Magnetic resonance imaging performed during hospitalization showed two patterns of pons involvement, which allowed the diagnosis of osmotic demyelination syndrome in addition to Wilson’s disease. Classic imaging findings were observed and illustrate perfectly these two conditions. We intend to highlight the important role of the radiologists in suggesting unforeseen diseases and the need for combined assessment by radiologists and neurologists in the establishment of proper diagnoses.

α-methylacyl-CoA racemase (AMACR) deficiency is a rare disorder, affecting peroxisomal metabolism of pristanic acid, with ten published adult cases. We describe an AMACR deficiency case with a clinical presentation dominated by episodic hyperCKaemia, suggesting that myopathic features of AMACR should be considered.

A novel pathogenic PYCR2 variant and corresponding brain images in two patients characterized by spastic paraplegia.