Nodding syndrome, an epidemic young-onset epilepsy-dementia complex in Uganda

Nodding syndrome (NS) is an enigmatic recurrent epidemic neurological disease that affects children in East Africa. The illness begins with nodding of the head and grand mal seizures that may lead to death after several years. The most recent outbreaks of NS occurred in northern Uganda and South Sudan. We describe the clinicopathologic spectrum of NS in Uganda. Ten children or young adults with NS were studied at autopsy and the neuropathological findings correlated with the onset, duration and progression of their neurological illness. All cases had epilepsy with grand mal seizures. Three cases had a clinical course that was predominantly characterized by epilepsy. Seven patients had progressive frontotemporal dementia. Two of the patients with dementia also had progressive quadriparesis. In all cases, the brain revealed tau pathology. In cases with an epilepsy-predominate course, the tau pathology was largely limited to the anterior frontal lobes but cases with dementia had more widespread cortical and subcortical tau pathology. In some cases, the histologic pattern was reminiscent of progressive supranuclear palsy. There are some interesting parallels between NS and the amyotrophic lateral sclerosis/Parkinson-dementia complex (ALS/PDC). The similarities are the presence of geographical isolates of disease manifesting in indigenous populations with familial clusters but no clear heritability. Both disorders appear to be related to an unknown environmental factor and both diseases appear to be fading over time in the respective geographical locations. One of the major open questions is whether ALS occurs in NS. This question will be addressed in future clinical studies and postmortem examination of the spinal cord. We propose that NS is a unique epilepsy-dementia complex in East Africa.LEARNING OBJECTIVESThis presentation will enable the learner to: 1.Describe the clinicopathologic features of a nodding syndrome.2.Compare the pathology of NS to ALS/PDC and related disease

Alzheimer’s Disease and Parkinson Dementia Distinguished by Cognitive Marker

Background Temporary memory binding (TMB) has been shown to be specifically affected by Alzheimer’s disease (AD) when it is assessed via free recall and titrating the task demands to equate baseline performance across patients. Methods Patients with Parkinson’s disease (PD) were subdivided into patients with and without cognitive impairment and compared with AD and amnestic mild cognitive impairment (aMCI) patients on their performance on the TMB. Results The results show that only patients with AD dementia present with impaired TMB performance. Receiver operating characteristic curve analyses showed that TMB holds high sensitivity and specificity for aMCI and AD relative to PD groups and healthy controls. Conclusion The TMB is sensitive to the neurodegenerative mechanisms leading to AD dementia but not to those underpinning PD dementia. As such, TMB task can aid the differential diagnosis of these common forms of dementia.

Fiber-specific white matter reductions in Parkinson hallucinations and visual dysfunction

ObjectiveTo investigate the microstructural and macrostructural white matter changes that accompany visual hallucinations and low visual performance in Parkinson disease, a risk factor for Parkinson dementia.MethodsWe performed fixel-based analysis, a novel technique that provides metrics of specific fiber-bundle populations within a voxel (or fixel). Diffusion MRI data were acquired from patients with Parkinson disease (n = 105, of whom 34 were low visual performers and 19 were hallucinators) and age-matched controls (n = 35). We used whole-brain fixel-based analysis to compare microstructural differences in fiber density (FD), macrostructural differences in fiber bundle cross section (FC), and the combined FD and FC (FDC) metric across all white matter fixels. We then performed a tract-of-interest analysis comparing the most sensitive FDC metric across 11 tracts within the visual system.ResultsPatients with Parkinson disease hallucinations exhibited macrostructural changes (reduced FC) within the splenium of the corpus callosum and the left posterior thalamic radiation compared to patients without hallucinations. While there were no significant changes in FD, we found large reductions in the combined FDC metric in Parkinson hallucinators within the splenium (>50% reduction compared to nonhallucinators). Patients with Parkinson disease and low visual performance showed widespread microstructural and macrostructural changes within the genu and splenium of the corpus callosum, bilateral posterior thalamic radiations, and left inferior fronto-occipital fasciculus.ConclusionsWe demonstrate specific white matter tract degeneration affecting posterior thalamic tracts in patients with Parkinson disease with hallucinations and low visual performance, providing direct mechanistic support for attentional models of visual hallucinations.

Simultaneous Stimulation of the Globus Pallidus Interna and the Nucleus Basalis of Meynert in the Parkinson-Dementia Syndrome

Background/Aim: The prevalence of cognitive symptoms in recently diagnosed Parkinson’s disease (PD) patients may be as high as 60%. We report a novel deep brain stimulation (DBS) strategy targeting both motor and cognitive symptoms. Methods: A PD patient diagnosed with mild cognitive impairment underwent DBS surgery targeting the globus pallidus interna (GPi; to treat motor symptoms) and the nucleus basalis of Meynert (NBM; to treat cognitive symptoms) using a single electrode per hemisphere. Results: Compared to baseline, 2-month follow-up after GPi stimulation was associated with motor improvements, whereas partial improvements in cognitive functions were observed 3 months after the addition of NBM stimulation to GPi stimulation. Conclusion: This case explores an available alternative for complete DBS treatment in PD, stimulating 2 targets at different frequencies with a single electrode lead.

Intravenous injection of l-BMAA induces a rat model with comprehensive characteristics of amyotrophic lateral sclerosis/Parkinson–dementia complex

Non-protein amino acid beta-N-methylamino-l-alanine (l-BMAA) is a neurotoxin that was associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinson–Dementia Complex (ALS/PDC) in Guam.