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

2021 ◽  
Vol 48 (s1) ◽  
pp. S5-S5
Author(s):  
MS Pollanen ◽  
S Onzivua
Keyword(s):  
East Africa ◽  
Indigenous Populations ◽  
List Type ◽  
Tau Pathology ◽  
Nodding Syndrome ◽  
Open Questions ◽  
Histologic Pattern ◽  
Grand Mal ◽  
Parkinson Dementia ◽  
Lateral Sclerosis

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

scholarly journals Subpial Thorn-shaped Astrocytes Are Prevalent In Guam ALS/PDC

2021 ◽  
Vol 48 (s2) ◽  
pp. S9-S10
Author(s):  
G.G. Kovacs ◽  
J.L. Robinson ◽  
D.P. Perl ◽  
V.M.Y. Lee ◽  
J.Q. Trojanowski
Keyword(s):  
Neurodegenerative Disorder ◽  
University Of Pennsylvania ◽  
List Type ◽  
Tau Pathology ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Cortical Regions ◽  
The University ◽  
Formalin Fixed ◽  
Lateral Sclerosis

Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex is a progressive neurodegenerative disorder characterized by neuronal and glial tau pathologies. With the aim to evaluate aging-related tau astrogliopathy (ARTAG) we examined the collection at the University of Pennsylvania, consisting of blocks of the frontal parietal, temporal, and occipital cortices. Formalin fixed, paraffin-embedded tissue blocks were evaluated using anti-tau antibodies PHF-1 and AT8. In addition to neuronal and oligodendroglial tau pathology, granular/fuzzy astrocytes in the gray matter and thorn-shaped astrocytes (TSAs) in subpial location were also observed. Twenty-one out of 33 cases (63%) showed subpial TSAs diffusely along the cortical surface in one or more cortical regions. Accumulation of TSAs in the depth of the sulci were seen in 41% in the temporal, 7% in the frontal and 14% in parietal cortex. This was not associated with perivascular neuronal tau pathology in the depth of the sulci. Accumulation of TSAs in the depth of cortical sulci in this cohort is approximately 20 times more frequent than reported in a European aging cohort. The presence of subpial TSAs in the depth of cortical sulci in CTE and Guam PDC, and less frequently in aging brains, might suggest common mechanisms.Learning ObjectivesDescribe the spectrum of neuropathology in Guam ALS/PDCDescribe the frequency of tau positive cortical subpial thorn-shaped astrocytes

scholarly journals A perspective on therapies for amyotrophic lateral sclerosis: can disease progression be curbed?

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiaojiao Xu ◽  
Dingding Shen ◽  
Yining Gao ◽  
Qinming Zhou ◽  
You Ni ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Disease Progression ◽  
Motor Neurons ◽  
Critical Role ◽  
Cell Therapies ◽  
Gene Therapies ◽  
Open Questions ◽  
Novel Therapeutic Strategies ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons, leading to paralysis and eventually death. Symptomatic treatments such as inhibition of salivation, alleviation of muscle cramps, and relief of spasticity and pain still play an important role in enhancing the quality of life. To date, riluzole and edaravone are the only two drugs approved by the Food and Drug Administration for the treatment of ALS in a few countries. While there is adequate consensus on the modest efficacy of riluzole, there are still open questions concerning the efficacy of edaravone in slowing the disease progression. Therefore, identification of novel therapeutic strategies is urgently needed. Impaired autophagic process plays a critical role in ALS pathogenesis. In this review, we focus on therapies modulating autophagy in the context of ALS. Furthermore, stem cell therapies, gene therapies, and newly-developed biomaterials have great potentials in alleviating neurodegeneration, which might halt the disease progression. In this review, we will summarize the current and prospective therapies for ALS.

scholarly journals Pathologic Thr175 tau phosphorylation in CTE and CTE with ALS

Neurology ◽  
2018 ◽  
Vol 90 (5) ◽  
pp. e380-e387 ◽  
Author(s):  
Alexander J. Moszczynski ◽  
Wendy Strong ◽  
Kathy Xu ◽  
Ann McKee ◽  
Arthur Brown ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Hippocampal Neurons ◽  
Glycogen Synthase ◽  
Chronic Traumatic Encephalopathy ◽  
Spinal Cord Tissue ◽  
Tau Pathology ◽  
Spinal Motor Neurons ◽  
Spinal Motor ◽  
Pathologic Features ◽  
Lateral Sclerosis

ObjectiveTo investigate whether chronic traumatic encephalopathy (CTE) and CTE with amyotrophic lateral sclerosis (CTE-ALS) exhibit features previously observed in other tauopathies of pathologic phosphorylation of microtubule-associated protein tau at Thr175 (pThr175 tau) and Thr231 (pThr231 tau), and glycogen synthase kinase–3β (GSK3β) activation, and whether these pathologic features are a consequence of traumatic brain injury (TBI).MethodsTau isoform expression was assayed by western blot in 6 stage III CTE cases. We also used immunohistochemistry to analyze 5 cases each of CTE, CTE-ALS, and 5 controls for expression of activated GSK3β, pThr175 tau, pThr231 tau, and oligomerized tau within spinal cord tissue and hippocampus. Using a rat model of moderate TBI, we assessed tau pathology and phospho-GSK3β expression at 3 months postinjury.ResultsCTE and CTE-ALS are characterized by the presence of all 6 tau isoforms in both soluble and insoluble tau isolates. Activated GSK3β, pThr175 tau, pThr231 tau, and oligomerized tau protein expression was observed in hippocampal neurons and spinal motor neurons. We observed tau neuronal pathology (fibrillar inclusions and axonal damage) and increased levels of pThr175 tau and activated GSK3β in moderate TBI rats.ConclusionsPathologic phosphorylation of tau at Thr175 and Thr231 and activation of GSK3β are features of the tauopathy of CTE and CTE-ALS. These features can be replicated in an animal model of moderate TBI.

From Kingdoms to Protectorate to New Nation

2019 ◽  
pp. 20-59
Author(s):  
David A. Hoekema
Keyword(s):  
Civil War ◽  
Middle East ◽  
East Africa ◽  
Slave Trade ◽  
Indigenous Populations ◽  
Northern Uganda ◽  
Ethnic Communities ◽  
Regional Control ◽  
History Of ◽  
New Nation

To set the background for the civil war in northern Uganda and the interfaith organization that was created to work for its resolution, the present chapter reviews the history of the region. Beginning with indigenous populations organized into kingdoms and ethnic communities, the slave trade that linked East Africa with the Middle East, and the competition among European powers for regional control, the chapter traces the transition from British protectorate to independent nation and the tumultuous period that followed, under the repressive regimes of Milton Obote and Idi Amin.

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

2016 ◽  
Vol 5 (1) ◽  
pp. 79-96 ◽  
Author(s):  
Ke-Wei Tian ◽  
Hong Jiang ◽  
Bei-Bei Wang ◽  
Fan Zhang ◽  
Shu Han
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Amino Acid ◽  
Intravenous Injection ◽  
Rat Model ◽  
Protein Amino Acid ◽  
High Incidence ◽  
Parkinson Dementia ◽  
Lateral Sclerosis

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.

scholarly journals Tau in the brain interstitial fluid is fragmented and seeding-competent

2020 ◽  
Author(s):  
Erica Barini ◽  
Gudrun Plotzky ◽  
Yulia Mordashova ◽  
Jonas Hoppe ◽  
Esther Rodriguez-Correa ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Interstitial Fluid ◽  
List Type ◽  
Fragmentation Pattern ◽  
Tau Pathology ◽  
Brain Areas ◽  
Brain Interstitial Fluid ◽  
Tau Aggregation ◽  
The Brain

SUMMARYIn Alzheimer disease, Tau pathology is thought to propagate from cell to cell throughout interconnected brain areas. However, the forms of Tau released into the brain interstitial fluid (ISF) in vivo during the development of Tauopathy and their pathological relevance remain unclear. Combining in vivo microdialysis and biochemical analysis, we find that human Tau (hTau) present in brain ISF is truncated and comprises at least 10 distinct fragments spanning the entire Tau protein. The fragmentation pattern is similar across different Tau transgenic models, pathological stages and brain areas. ISF hTau concentration decreases during Tauopathy progression, while its phosphorylation increases. ISF from mice with established Tauopathy induces Tau aggregation in HEK293-Tau biosensor cells and notably, only a small fraction of Tau, separated by ultracentrifugation, is seeding competent. These results indicate that only a subset of Tau accounts for ISF seeding competence and have the potential to contribute to the propagation of Tau pathology.Graphical abstractHighlights✓In transgenic mice, interstitial fluid comprises several Tau fragments spanning the entire Tau sequence.✓Interstitial fluid Tau concentration decreases with Tauopathy progression, while phosphorylation increases.✓Only interstitial fluid from mice with established Tauopathy is seeding competent in vitro.✓Interstitial fluid seeding competence is driven by less soluble, aggregated and phosphorylated Tau species.In BriefBarini et al. show that in the brain interstitial fluid of Tau transgenic mice, truncated Tau decreases, while its phosphorylation increases during the progression of pathology. A subset of less soluble, aggregated and phosphorylated ISF Tau induces Tau aggregation in cells.

scholarly journals A commonly overlooked motor neuron disease mimicker

2014 ◽  
Vol 2014 ◽  
Author(s):  
Manas Ghosh ◽  
Ambarish Bhattacharya ◽  
Kaushik Ghosh ◽  
Atri Chatterjee ◽  
Sisir Chakraborty ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Electrolyte Imbalance ◽  
List Type ◽  
Parathyroid Surgery ◽  
The Common ◽  
Work Up ◽  
Treatable Condition ◽  
Learning Points ◽  
Lateral Sclerosis

Summary Motor neuron disease (MND) is a progressive devastating neurodegenerative disease, which universally progresses towards death. Hence, every attempt should be made to find out if there are any treatable conditions, which can mimic MND. Herein, we describe a case of hypercalcaemia due to primary hyperparathyroidism confused as MND and subsequently cured with parathyroid surgery. Learning points Any patient with neurological disorder should have a screening of all the common electrolytes including calcium as electrolyte imbalance can present with paralysis (e.g. hypokalaemia) to amyotrophic lateral sclerosis (e.g. hypercalcaemia). No patient should be stamped as having MND without having a proper work-up of all its differentials as there might be a treatable condition masquerading as MND.

scholarly journals SPiQE: an automated analytical tool for detecting and characterising fasciculations in amyotrophic lateral sclerosis

2019 ◽  
Author(s):  
J Bashford ◽  
A Wickham ◽  
R Iniesta ◽  
E Drakakis ◽  
M Boutelle ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Classification Accuracy ◽  
Surface Emg ◽  
Analytical Tool ◽  
High Density ◽  
List Type ◽  
Motor Neuropathy ◽  
Density Surface ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractOBJECTIVESFasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). Compared to concentric needle EMG, high-density surface EMG (HDSEMG) is non-invasive and records fasciculation potentials (FPs) from greater muscle volumes over longer durations. To detect and characterise FPs from vast data sets generated by serial HDSEMG, we developed an automated analytical tool.METHODSSix ALS patients and two control patients (one with benign fasciculation syndrome and one with multifocal motor neuropathy) underwent 30-minute HDSEMG from biceps and gastrocnemius monthly. In MATLAB we developed a novel, innovative method to identify FPs amidst fluctuating noise levels. One hundred repeats of 5-fold cross validation estimated the model’s predictive ability.RESULTSBy applying this method, we identified 5,318 FPs from 80 minutes of recordings with a sensitivity of 83.6% (+/-0.2 SEM), specificity of 91.6% (+/-0.1 SEM) and classification accuracy of 87.9% (+/-0.1 SEM). An amplitude exclusion threshold (100μV) removed excessively noisy data without compromising sensitivity. The resulting automated FP counts were not significantly different to the manual counts (p=0.394).CONCLUSIONWe have devised and internally validated an automated method to accurately identify FPs from HDSEMG, a technique we have named Surface Potential Quantification Engine (SPiQE).SIGNIFICANCELongitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.HighlightsSPiQE combines serial high-density surface EMG with an innovative signal-processing methodologySPiQE identifies fasciculations in ALS patients with high sensitivity and specificityThe optimal noise-responsive model achieves an average classification accuracy of 88%

Sign in / Sign up

Export Citation Format

Share Document