Asymmetric Parkinsonism Research Articles

Comparing classic-onset corticobasal syndrome to speech/language-onset corticobasal syndrome

IntroductionPatients with classic-onset corticobasal syndrome (CBS) present with asymmetric limb apraxia and parkinsonism. We have, however, observed patients who initially present with speech and/or language (SL) problems and several years later develop CBS (i.e., SL-onset CBS). We aimed to compare clinical, neuroimaging and pathological characteristics of classic-onset CBS with SL-onset CBS. MethodsWe conducted a retrospective cohort study of 62 patients who met criteria for CBS (17 presented with classic-onset CBS and 45 had SL-onset CBS). We compared demographics, clinical characteristics, and grey and white matter volume loss with SPM12 between groups and assessed pathology and corticobasal degeneration (CBD) pathological lesion counts in patients who had died and undergone autopsy. ResultsMedian age at CBS diagnosis was 66.4 years in classic-onset CBS and 73.6 years in SL-onset CBS. Classic-onset CBS had higher frequencies of dystonia, myoclonus, and alien limb phenomenon, while SL-onset CBS had a higher frequency of vertical supranuclear gaze palsy. Both groups showed smaller frontoparietal volumes than controls, with SL-onset CBS having greater volume loss in the left supplementary motor area than classic-onset CBS. All three classic-onset CBS cases with autopsy (100 %) had CBD pathology while 8/21 of SL-onset CBS cases (38 %) had CBD. Pathological lesion burden (including astrocytic plaques) did not differ between classic-onset and SL-onset CBS. ConclusionClassic-onset and SL-onset CBS appear to be different syndromes, with the former being a more profuse motor syndrome. The more widespread volume loss in SL-onset CBS likely reflects longer disease course.

Levodopa-Induced Dyskinesias in Corticobasal Degeneration: A Case Report and Review of the Literature

Corticobasal degeneration (CBD) is a neurodegenerative disorder characterized by several clinical features, including progressive asymmetric parkinsonism, dystonia, myoclonus and cortical sensory signs. This clinical presentation is referred to as Corticobasal Syndrome (CBS), considering the diverse underlying pathologies associated CBS.

Interhemispheric reactivity of the subthalamic nucleus sustains progressive dopamine neuron loss in asymmetrical parkinsonism

Parkinson's disease (PD) is characterized by the progressive and asymmetrical degeneration of the nigrostriatal dopamine neurons and the unilateral presentation of the motor symptoms at onset, contralateral to the most impaired hemisphere. We previously developed a rat PD model that mimics these typical features, based on unilateral injection of a substrate inhibitor of excitatory amino acid transporters, L-trans-pyrrolidine-2,4-dicarboxylate (PDC), in the substantia nigra (SN). Here, we used this progressive model in a multilevel study (behavioral testing, in vivo 1H-magnetic resonance spectroscopy, slice electrophysiology, immunocytochemistry and in situ hybridization) to characterize the functional changes occurring in the cortico-basal ganglia-cortical network in an evolving asymmetrical neurodegeneration context and their possible contribution to the cell death progression. We focused on the corticostriatal input and the subthalamic nucleus (STN), two glutamate components with major implications in PD pathophysiology. In the striatum, glutamate and glutamine levels increased from presymptomatic stages in the PDC-injected hemisphere only, which also showed enhanced glutamatergic transmission and loss of plasticity at corticostriatal synapses assessed at symptomatic stage. Surprisingly, the contralateral STN showed earlier and stronger reactivity than the ipsilateral side (increased intraneuronal cytochrome oxidase subunit I mRNA levels; enhanced glutamate and glutamine concentrations). Moreover, its lesion at early presymptomatic stage halted the ongoing neurodegeneration in the PDC-injected SN and prevented the expression of motor asymmetry. These findings reveal the existence of endogenous interhemispheric processes linking the primary injured SN and the contralateral STN that could sustain progressive dopamine neuron loss, opening new perspectives for disease-modifying treatment of PD.

Arm Swing while Walking and Running: A New Clinical Feature to Separate Parkinson's Disease from Functional Parkinsonism.

Functional parkinsonism is an important differential diagnosis of Parkinson's disease (PD). Based on anecdotal experience, we hypothesized that arm swing while walking and running could differentiate these two conditions, but this assumption has not been previously explored systematically. To examine differences in arm swing while walking and running between patients with PD and functional parkinsonism. We analyzed blinded video assessments of arm swing and other gait parameters in patients with asymmetrical PD (n = 81) and functional parkinsonism (n = 8) while walking and running. The groups were matched for age, sex and disease duration. In contrast to those with PD, patients with functional parkinsonism (i) were more likely to have a marked asymmetry in arm swing while walking (5/8 vs. 25/81; P = 0.06), (ii) were less likely to improve arm swing while running with full effort (3/8 vs. 72/81; P < 0.001) and (iii) demonstrated normal passive arm swing even when asymmetry of arm swing was marked during running/walking (6/6 vs. 9/33; P = 0.002). Assessment of arm swing while walking and running and passive arm swing could be important differentiating clinical features between functional parkinsonism and PD.

Asymmetrical parkinsonism due to novel WDR45 variant with beta-propeller protein-associated neurodegeneration (BPAN).

Beta-propeller protein-associated neurodegeneration (BPAN) encompasses a group of refractory neurodegenerative diseases that are caused by excessive iron deposition in the brain, especially in the basal ganglia. We reported a case of BPAN with a novel variant of the WDR45 gene at Xp11.23. Our patient was a 31-year-old woman who has had an intellectual disability since childhood. Approximately 3 years ago, she developed asymmetric parkinsonism affecting the distal right upper and lower limbs. Consistent with her neurological findings, dopamine transporter single-photon emission computed tomography demonstrated the differences between the left and right sides. She was diagnosed as BPAN according to genetic analysis, which showed a novel heterozygous variant (c.345-3C>G) in WDR45. To the best of our knowledge, only a few previous case reports on asymmetric BPAN have described the quantitative differences in neuroimaging parameters between the left and right sides. These neuroimaging features were similar to those of Parkinson's disease, among the other neurodegenerative diseases. Our report may provide clues to elucidate the pathological mechanism of BPAN which is a refractory neurodegenerative disease.

Corticobasal syndrome mimicking Foix-Chavany-Marie syndrome with suggested 4-repeat tauopathy by tau PET

BackgroundCorticobasal syndrome (CBS) is a neurodegenerative disease diagnosed based on clinical manifestations such as asymmetrical parkinsonism, limb apraxia, and speech and language impairment. The background pathology of CBS is commonly a variety of proteinopathies, but association with cerebrovascular disease has also been reported. Foix-Chavany-Marie syndrome (FCMS) is a rare neurological disorder characterized by facio-pharyngo-glossal diplegia with automatic-voluntary movement dissociation presenting with bilateral paresis of the facial, lingual, pharyngeal and masticatory muscles. FCMS is commonly attributable to stroke. Transactive response DNA binding protein of 43 kD (TDP-43) proteinopathy is also known as the pathological background of FCMS, while the pathological background of the majority of CBS cases consists of diverse tauopathies instead of TDP-43 proteinopathy. In this report, we describe a case mimicking FCMS that was finally diagnosed as CBS with suggested 4-repeat tauopathy.Case presentationA 68-year-old female started experiencing difficulty speaking followed by difficulty writing, and especially texting, several years before her visit. Her impairment had been gradually worsening, and she came to our hospital. On neurological examination, she demonstrated the facial apraxia, frontal lobe dysfunction, and upper motor neuron signs. She presented some characteristics suggestive of FCMS. Her symptoms exhibited rapid progression and myoclonus, parkinsonism, and left-side dominant cortical sensory deficit occurred, resulting in the fulfillment of diagnostic criteria for CBS after 9 months. Tau PET imaging displayed notable ligand uptake in the brainstem, subthalamic nuclei, basal ganglia, and bilateral subcortical frontal lobe, suggesting that her pathological background was 4-repeat tauopathy. As a result of her progressive dysphagia, she became unable to eat and passed away after 12 months.ConclusionWe hereby present an atypical case of CBS showing clinical features mimicking FCMS at first presentation. TDP-43 proteinopathy was suspected based on the clinical symptoms in the early stages of the disease; however, the clinical course and imaging findings including tau PET suggested that her pathological background was 4-repeat tauopathy.

The prioritization of biomarkers in the diagnostic workup of motor tauopathy

AbstractMotor tauopathies represent a spectrum of degenerative, poorly levodopa‐responsive parkinsonisms unified by the pathological accumulation of hyperphosphorylated tau protein fragments in the brain. The principal entities, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are rare conditions (&lt;10 per 100,000) and present with non‐amnestic cognitive impairment ‐ mostly involving frontal‐subcortical networks – in around 40% of patients at baseline. Additionally, the phenotypic PSP spectrum expresses with oculomotor dysfunction, falls and bulbar symptoms at varying degrees. On the other hand, CBD tauopathy is the most frequent aetiology underlying the corticobasal syndrome (CBS) that is a multifaceted disorder characterized by a markedly asymmetric Parkinsonism with apraxia and neocortical deficits. Paralleling the clinical symptoms, the distribution of functional and metabolic impairment specifically involves different brain regions in PSP and CBD. Hence, metabolism assessment by FDG‐positron emission tomography (PET) allows for accurate distinction of motor tauopathies from other parkinsonisms or one with another (AUC 0.80 and 0.92‐0.97, respectively). In this context, the European Intersociety Consensus Diagnostic Task Force recommends the use of FDG‐PET as the first‐level diagnostic biomarker to achieve early and accurate differential diagnosis of motor tauopathies. Afterwards, the assessment of CSF biomarkers of Alzheimer’s disease (AD) is advised to identify that minority of cases of CBS underpinned by an AD aetiology (10‐20%). With this sequence of biomarkers, the diagnostic workflow aims to an early identification of motor tauopathies and advocates in‐depth etiological investigation of CBS where access to AD‐specific drugs, when available, should be considered in a non‐negligible proportion of patients.

The Role of Dual-Phase 18 F-FP-CIT PET to Early Diagnosis of Corticobasal Syndrome.

Corticobasal syndrome (CBS) is a neurodegeneration characterized by asymmetric parkinsonism, dystonia, myoclonus, and apraxia. In the early stage, CBS presents with asymmetric parkinsonism and cortical symptoms (apraxia and alien hand), and neuroimaging finding is often vague, making early clinical differentiation from idiopathic Parkinson disease (IPD) challenging. This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter (DAT) uptake using dual-phase FP-CIT PET in discriminating between CBS and IPD at early stage. The study enrolled clinically diagnosed CBS (n = 11) and IPD (n = 22) patients (age and sex matched). All participants underwent dual-phase 18 F-FP-CIT PET, and regional SUV ratio (SUVR) was obtained by semiquantitative analysis. The early perfusion imaging and DAT imaging were compared between groups. The regional SUVRs (early phase) of the frontal lobe, thalamus, cingulate, and caudate were significantly lower in patients with CBS, whereas the SUVR of occipital lobe was lower in the IPD group. The CBS group exhibited more prominent asymmetry than the IPD group, particularly in the perirolandic area, superior frontal gyrus, and anterior parietal lobe in early phase PET. Striatal DAT uptake (delayed phase) revealed that the caudate showed lower SUVR and prominent asymmetry in the CBS group, and the caudate-to-putamen ratio (CP ratio) was significantly lower in CBS patients ( P < 0.001). Among the parameters (early and delayed), the CP ratio in DAT exhibited the most powerful discriminative power from receiver operating characteristic curve comparison (area under curve = 0.983). This study demonstrated that the dual-phase FP-CIT PET is useful in differentiating CBS and IPD in the early stage of the disease, and a lower CP ratio of DAT imaging is highly informative for distinguishing between corticobasal degeneration and IPD.

Hemiatrophy of The Cerebral Hemisphere with Contralateral Cerebellar Atrophy: A Case Report

Childhood cerebral hemiatrophy is a rare clinical condition. Its causes are numerous, but they can be divided into two categories: congenital and acquired. The congenital type develops intrauterine, whereas the acquired type develops early in life, usually before the age of two. Cerebral hemiatrophy syndromes are characterized by a wide range of neurological symptoms. Childhood epilepsy, mental retardation, and neuropsychiatric disorders are common, whereas movement disorders such as highly asymmetric parkinsonism or hemidystonia, as well as neuropsychiatric problems, have been reported in adults. Here we present a 22-year-old patient who presented with refractory seizure. Imaging findings showed hemiatrophy of the right cerebral hemisphere with left cerebellar atrophy.

Clinicoradiologic and Neuropathologic Evaluation of Corticobasal Syndrome.

Corticobasal syndrome (CBS) is a clinical phenotype characterized by asymmetric parkinsonism, rigidity, myoclonus, and apraxia. Originally believed secondary to corticobasal degeneration (CBD), mounting clinicopathologic studies have revealed heterogenous neuropathologies. The objectives of this study were to determine the pathologic heterogeneity of CBS, the clinicoradiologic findings associated with different underlying pathologies causing CBS, and the positive predictive value (PPV) of current diagnostic criteria for CBD among patients with a CBS. Clinical data, brain MRI, and neuropathologic data of patients followed at Mayo Clinic and diagnosed with CBS antemortem were reviewed according to neuropathology category at autopsy. The cohort consisted of 113 patients with CBS, 61 (54%) female patients. Mean ± SD disease duration was 7 ± 3.7 years; mean ± SD age at death was 70.5 ± 9.1 years. The primary neuropathologic diagnoses were 43 (38%) CBD, 27 (24%) progressive supranuclear palsy (PSP), 17 (15%) Alzheimer disease (AD), 10 (9%) frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein 43 (TDP) inclusions, 7 (6%) diffuse Lewy body disease (DLBD)/AD, and 9 (8%) with other diagnoses. Patients with CBS-AD or CBS-DLBD/AD were youngest at death (median [interquartile range]: 64 [13], 64 [11] years) while CBS-PSP were oldest (77 [12.5] years, p = 0.024). Patients with CBS-DLBD/AD had the longest disease duration (9 [6] years), while CBS-other had the shortest (3 [4.25] years, p = 0.04). Posterior cortical signs and myoclonus were more characteristic of patients with CBS-AD and patients with CBS-DLBD/AD. Patients with CBS-DLBD/AD displayed more features of Lewy body dementia. Voxel-based morphometry revealed widespread cortical gray matter loss characteristic of CBS-AD, while CBS-CBD and CBS-PSP predominantly involved premotor regions with greater amount of white matter loss. Patients with CBS-DLBD/AD showed atrophy in a focal parieto-occipital region, and patients with CBS-FTLD-TDP had predominant prefrontal cortical loss. Patients with CBS-PSP had the lowest midbrain/pons ratio (p = 0.012). Of 67 cases meeting clinical criteria for possible CBD at presentation, 27 were pathology-proven CBD, yielding a PPV of 40%. A variety of neurodegenerative disorders can be identified in patients with CBS, but clinical and regional imaging differences aid in predicting underlying neuropathology. PPV analysis of the current CBD diagnostic criteria revealed suboptimal performance. Biomarkers adequately sensitive and specific for CBD are needed.

69-Year-Old Female with Progressive Supranuclear Palsy, Frontotemporal Dementia, Focal Hyperkinesia and one variant in the GCH1 gene and in the CSF1R gene

How insignificant is the detection of gene variants in a novel clinical presentation of an atypical Parkinson’s syndrome with positive family history? We present the case of a 69-year-old woman with Progressive Vertical Supranuclear Palsy (PSP), focal hyperkinesia, non-L-dopa-responsive asymmetrical Parkinsonism, postural instability as well as apraxia, cognitive, speech and frontal disorder, with a positive family history, MRI evidence of mesial temporal atrophy and tau-PET evidence of tau pathology as well as identification of one variant in the GCH1 gene and one variant in the CSF1R gene. The fact that the clinical presentation and radiological finding of our patients are not compatible with a known and well described genetic disorder caused by pathogenic mutations of these genes, supports the notion that the detected gene variants have an uncertain significance in the pathogenesis of our patient’s disease. Nevertheless, the novel description of the phenotype of our case of PSP with frontal lobe features, focal hyperkinesia and a positive family history, points to an in-vivo tauopathy, in which a genetic burden may play a role. The follow-up of the patient und her family may offer further insights into the pathophysiology of complex neurodegenerative diseases in the spectrum of tauopathies, offering possible new therapeutic targets.

Clinico-radiologic and Pathological Evaluation of Corticobasal Syndrome (S8.004)

Clinico-radiologic and Pathological Evaluation of Corticobasal Syndrome (S8.004)

Two Different PRKN Compound Heterozygous Variants Combinations in the Same Family.

Two Different PRKN Compound Heterozygous Variants Combinations in the Same Family.

Rapidly Progressive Corticobasal Degeneration Mimicking Brainstem Encephalitis.

Corticobasal degeneration (CBD) may have a rapidly progressive (RP) clinical course, mimicking other neurological conditions. To describe a neuropathologically proven case of RP-CBD in a patient initially diagnosed with immune-mediated brainstem encephalitis. Retrospective data collection from electronic records and authorized video material. A 51-year-old man presented with bilateral ptosis, diplopia, and dysphagia. The diagnostic workup was negative for myasthenic syndromes. He progressively developed cognitive dysfunction with frontal release signs and asymmetric parkinsonism. Cerebrospinal fluid evaluation revealed 4 leukocytes/uL, 0.32 g/L proteins, 0.85 g/L glucose, and absent oligoclonal bands. Weakly positive anti-PNMA2 (Ma2/Ta) antibodies were present, and magnetic resonance imaging showed a T2 hyperintensity involving the midbrain and pons. Based on these features, the diagnosis of immune-mediated brainstem encephalitis was considered. The patient did not improve after several cycles of methylprednisolone, intravenous immunoglobulin, and plasma exchange. At 1 year after onset, he developed horizontal and vertical gaze limitation and worsening of the parkinsonism and cognitive dysfunction. By age 53, he was severely disabled, requiring percutaneous gastrostomy for feeding. Anti-IgLON5 was negative. He fulfilled the clinical criteria for probable progressive supranuclear palsy. He died from pneumonia at age 54. The neuropathological examination revealed a 4-repeat tauopathy with features of CBD with extensive involvement of the brainstem. RP-CBD may resemble brainstem encephalitis. The severity of brainstem and upper spinal cord pathology in the postmortem examination correlated with the clinical and imaging features.

Tau PET imaging with 18F‐PI‐2620 in patients with corticobasal syndrome: a case series

AbstractBackgroundCorticobasal syndrome (CBS) is the clinical phenotype originally described for corticobasal degeneration (CBD), a rare sporadic neurodegenerative 4‐repeat tauopathy, clinically characterized by the presence of asymmetric parkinsonism, apraxia, cortical sensory deficits, dystonia, myoclonus, and cognitive dysfunction. However, patients with CBS can have neurodegenerative pathology other than CBD, like progressive supranuclear palsy (PSP), Alzheimer's Disease (AD), Vascular Dementia, and Lewy body dementia. Selective tau tracers have made it possible to detect the presence of abnormal tau deposits in vivo. 18F‐PI‐2620 is a tau‐specific positron emission tomography (PET) tracer with a high binding affinity for aggregated tau. This study aims to investigate the potential role of 18F‐PI‐2620 as a biomarker in patients with CBS.MethodFour participants with clinical features consistent with probable CBS according to the 2013 Armstrong diagnostic criteria underwent dynamic PET scans for 75 min after injection of 18F‐PI‐2620. Specific binding ratios were derived from averaged PET images from 45‐75 min post‐injection.ResultFirst two patients had robust increases in 18F‐PI‐2620 uptake in temporal, parietal, and occipital cortical regions with relative sparing of globus pallidus and putamen. In the third patient, 18F‐PI‐2620 uptake was observed in the globus pallidus and putamen with relative sparing of cortical regions. The fourth patient had low 18F‐PI‐2620 uptake localized in the globus pallidus, temporal, and parietal regions.ConclusionIn the first two patients, 18F‐PI‐2620 binding distribution resembles what was described for Alzheimer's disease. In the third patient, 18F‐PI‐2620 uptake pattern suggests PSP. In this particular case, we hypothesize the definitive diagnosis is PSP‐CBS, a rare clinical presentation of PSP with CBS features. Finally, the fourth patient had low 18F‐PI‐2620 uptake but in areas clearly related to AD, PSP, and probably CBD. Our findings support CBS's heterogeneous pathological basis and suggest that 18F‐PI‐2620 could represent a valuable tool in the assessment of CBS, establishing an underlying tauopathy in most cases. However, we suspect 18F‐PI‐2620 in CBS is insufficient to distinguish, in some cases, AD pathology from other tauopathies. Therefore, the use of additional biomarkers to establish the presence of amyloid pathology should be considered. Further studies are needed to confirm these preliminary results.

Clinicopathological features of progressive supranuclear palsy with asymmetrical atrophy of the superior cerebellar peduncle.

Progressive supranuclear palsy (PSP) can be diagnosed despite the presence of asymmetrical parkinsonism depending on the clinical diagnostic criteria. Some studies have reported that atrophy of the superior cerebellar peduncle (SCP) is more frequent in PSP than in Parkinson's disease. There have also been reports of PSP cases with an asymmetrically atrophic SCP. Therefore, we analyzed 48 specimens from consecutive autopsy cases that were neuropathologically diagnosed as PSP to investigate the laterality of brain lesions, including the SCP. We measured the width of the SCP and evaluated the laterality of atrophy. We semi-quantitatively evaluated neuronal loss, atrophy/myelin pallor, and tau pathology in three steps. Asymmetrical atrophy of the SCP was present in seven (14.6%) of 48 cases. The atrophic side of the SCP corresponded to the dominant side of the tau pathology in the cerebellar dentate nucleus. It was opposite to the dominant side of the myelin pallor and tau pathology in the red nucleus and of the tau pathology in the central tegmental tract and inferior olivary nucleus, coinciding with the neurologically systematic anatomy of the Guillain-Mollaret triangle. Neurodegeneration of PSP can progress asymmetrically from one side to the initially intact side in PSP with an initial predominance of Richardson's syndrome, progressive gait freezing, ocular motor dysfunction, parkinsonism, or corticobasal syndrome. To our knowledge, no previous study has reported asymmetrical PSP neuropathology; this is the first study to report the presence of PSP cases with asymmetrical SCP atrophy and systematically asymmetrical degeneration of the Guillain-Mollaret triangle.

The Role of Focused Ultrasound in the Management of Movement Disorders: Insights after 5 Years of Experience.

The Role of Focused Ultrasound in the Management of Movement Disorders: Insights after 5 Years of Experience.

Ayurvedic Management Successfully Reduces Dose of L-Dopa and Remission of Symptoms in Parkinson’s Disease – (A Case Report)

&lt;strong&gt;Background and Aim:&lt;/strong&gt; Parkinson's Disease (PD) is a neurodegenerative condition of motor nervous system. The symptoms of PD are similar to &lt;em&gt;KampaVata&lt;/em&gt; (a disease of &lt;em&gt;Vata Dosha&lt;/em&gt;) such as &lt;em&gt;Karapadatala kampa&lt;/em&gt; (tremors in hands and foot), &lt;em&gt;Dehabhramana&lt;/em&gt; (postural instability), &lt;em&gt;Nidrabhagna&lt;/em&gt; (insomnia) and &lt;em&gt;Matiksheena&lt;/em&gt; (dementia) referred by Ayurvedic classics. The most effective management of PD in Allopathic system is dopamine replacement therapy but long-term use of L-Dopa is associated with motor complications. Available medications for PD provides only symptomatic relief and there is no treatment proven to cure the disease or delay its progression. The present case report is a known case of young onset asymmetric Parkinsonism who was on 700mg L-Dopa, managed with Ayurveda therapies. The line of treatment included &lt;em&gt;Vatanulomana&lt;/em&gt; (pacifying morbid VataDosa), &lt;em&gt;Srotoshodhana&lt;/em&gt; (clearing of the obstructed bodychannels) and &lt;em&gt;Rasayana&lt;/em&gt; (rejuvenation). &lt;strong&gt;Management and results:&lt;/strong&gt; It included both internal and external Ayurveda therapies. Therapies were performed every year for around 20 days in 3 consecutive years. The assessment was done by Parkinson’s disease questionnaire 39 and Schwab and England Activities of daily Living scale. Reduction in the dose of L-Dopa, improvement in tremor, bradykinesia, rigidity, regaining the perception of taste and smell was observed at the end of 3 years of treatment. &lt;strong&gt;Conclusion:&lt;/strong&gt; The dose of L-Dopa was reduced from 700mg to 100mg/day and the quality of life improved.

Dementia with Lewy bodies: A differential diagnosis of normal pressure hydrocephalus

AbstractBackgroundThe diagnosis of idiopathic normal pressure hydrocephalus (NPH) is challenging and remains overestimated because of the absence of specific clinical, imaging or biological features. It relies on association of classical triad of symptoms (gait disturbance, cognition impairment, urinary symptoms) associated to a ventricular enlargement. Several differential diagnoses should be considered with an initial presentation suggestive of NPH, such as dementia with Lewy bodies (DLB), Alzheimer disease (AD) and vascular dementia (VD). The aim of this study was to identify NPH differential diagnosis as well as to highlight clinical and radiological features that could help questioning this diagnosis, before performing invasive procedures.MethodIn this monocentric retrospective study, we included 42 patients fulfilling the criteria of possible NPH on initial presentation. At the end of the follow‐up, we classified the sample into patients with probable NPH (NPH group ; n = 13), differential diagnosis of NPH (NPH‐ group; n = 21) and dual pathology with criteria of probable NPH (NPH+; n = 8), depending on their outcome after cerebrospinal fluid (CSF) drainage. We collected clinical data, including results of cognitive assessment, as well as results of CSF biomarkers, EEG, functional and morphological neuroimaging. Ventricular enlargement profile was analyzed using different visual measures on MRI.ResultThe main differential diagnosis of NPH was DLB (21/21), mixed with vascular dementia in four cases. None of the patient had a CSF profile suggestive of AD. Regarding clinical features, asymmetric parkinsonism, fluctuations, agitation during sleep, visual hallucinations and visuospatial impairment were significantly more frequent in NPH‐ patients, compared to NPH patients (p=0.033). The callosal angle was significantly more acute (&lt;104° ; p &lt;0.01) and fourth ventricular dilatation greater (&gt;17 mm ; p&lt;0.01) in NPH patients than in NPH‐ patients, while there was no significant difference in the dilatation of lateral ventricles and third ventricle.ConclusionDLB appeared as the main differential diagnosis of NPH. Our results indicate that the existence of asymmetric parkinsonism, fluctuations, agitation during sleep, visual hallucinations or visuospatial impairment, as well as the absence of acute callosal angle or fourth ventricular dilatation should lead to consider DLB as a differential diagnosis of NPH.

Multiple pathologies in an amateur soccer player with severe chronic traumatic encephalopathy

AbstractBackgroundChronic traumatic encephalopathy (CTE) is a tauopathy associated with repeated brain injuries. The presence of co‐pathologies is not uncommon in individuals with CTE. Here, we described clinical and neuropathological findings of amateur soccer with a history of progressive parkinsonism and dementia.Method63‐years old male with no family history of neurodegenerative disease or alcohol abuse. He played amateur soccer as a goalkeeper for 42 years. Episode of concussion with loss of conciseness at age of 20, without symptoms afterward. He denied any non‐soccer related episodes of brain trauma. At the age of 65, he started with REM behavior disorder, followed by apathy. At age 67, he developed asymmetric bradykinesia, limb rigidity, and complete anosmia. At the age of 73, a neurological examination demonstrated asymmetric parkinsonism, worse in the left. He denied motor fluctuations or hallucinations. At age 75, cognitive impairment was observed and his MMSE score was 22/30 with temporal disorientation, executive and delayed recall impairments. The working diagnosis was Parkinson's disease dementia. He died at age of 81.ResultNeuropathological examination showed prominent frontal and temporal atrophy, hippocampal asymmetry and moderate depigmentation of substantia nigra, and locus coeruleus. Hematoxylin and eosin staining showed left hippocampal sclerosis and white matter arteriolosclerosis. Immunohistochemistry evaluation showed aggregates of hyperphosphorylated tau in neurons, astrocytes and cell processes in a patch distribution around vessels, with deep sulcal accentuation in several cortical regions fulfilling criteria for CTE stage III. Additionally, neurofibrillary pathology was found in subcortical and cortical areas (BRAAK stage V) and Aß plaques were distributed in cortical, limbic and diencephalon areas (Thal 4), altogether meeting criteria for an intermediated ADNC. Also, phosphorylated TDP‐43 immunoreactive dot‐like and neuronal cytoplasmatic inclusions were found in entorhinal cortex, amygdala and hippocampus (LATE stage 3). Moreover, diffuse Lewy pathology was observed (Braak 5 of Parkinson´s disease).ConclusionDespite showing multiple co‐pathologies, former soccer players may develop CTE changes. This case adds to the increased number of former soccer players showing dementia due to multiple pathologies and CTE. If soccer‐related brain trauma triggers multiple neuropathological processes or if they develop independently remains an open question.