Alien Hand Research Articles

Essential thrombocythemia complicated by multivessel intracranial dolichoectasia with subarachnoid hemorrhage and recurrent cerebral infarction

BackgroundPatients with essential thrombocythemia (ET) can develop systemic thrombotic and hemorrhagic vascular complications due to increased and dysfunctional platelets.Case presentationWe encountered a 49-year-old Japanese woman with a history of essential ET, cerebral infarction, hypertension, and hyperlipidemia. She had been taking anagrelide (2.5 mg/day) and aspirin (100 mg/day) and had vomited at home. At the time of admission to our hospital, she was in a deep stupor. We thought these symptoms were caused by intracranial hypertension. Head computed tomography showed severe subarachnoid hemorrhage (SAH) at the interhemispheric fissure, hematoma at the corpus callosum, and intraventricular hemorrhages. Digital subtraction angiography demonstrated multiple dilated, stenotic, tortuous intracranial arteries, and a dissecting aneurysm at the right anterior cerebral artery (ACA). The dissecting aneurysm measured 7.7 × 15.5 mm, and a bleb was observed. Our diagnosis was ruptured ACA dissecting aneurysm and diffuse intracranial arterial dolichoectasia (DIADE). We performed stent-assisted coil embolization of the aneurysm. She remained apathetic and manifested unilateral apraxia and alien limb syndrome due to a partial callosal disconnection. Two months thereafter her symptoms gradually improved, her consciousness level and limb function improved, and her modified Rankin scale (mRS) score was 2. However, when we tapered her antiplatelet therapy, she again developed an acute cerebral infarct.ConclusionsThis is the first presentation of a patient with ET complicated by DIADE, both of which can result in ischemic and hemorrhagic vascular complications including SAH. As antithrombotic therapy in patients with DIADE and ET may be associated with higher hemorrhage rates, its effects must be monitored carefully.

B - 11 Alien Limb and Corticobasal Degeneration: a Neuropsychological Case Study

Abstract Objective The patient presented with alien limb, frequently associated with corticobasal degeneration, an atypical parkinsonian syndrome with rigidity, akinesia, dystonia, cortical sensory deficit, and apraxia. Subjective memory complaints are also common. Neuropsychological performance typically includes poor performance on verbal fluency and measures tapping into executive functioning, but confrontation naming and verbal comprehension are initially well-preserved. Method The patient is a right-handed 69-year-old male who developed the sensation of alien limb in his left arm 2 years prior, in which his left hand did not feel “real.” Additionally, the patient presented with memory difficulties, mild word-finding problems, and physical/motor complaints (i.e., limb apraxia, tremor, bradykinesia, occasional limb dystonia, and postural instability) for approximately 2 years. The patient sought neuropsychological assessment to clarify his cognitive functioning in light of his neurologic symptoms. Results Premorbid functioning was in the exceptionally high range, with 18 years of education. Neuropsychologically, immediate memory was generally average, and generally low average delayed memory and recognition abilities. Mild inefficiencies were observed in executive functioning and semantic fluency. Otherwise, the patient performed generally average across other tasks of language, including confrontation naming, and attention. Conclusions In light of the literature, it is expected that corticobasal degeneration will be associated with subjective memory difficulties, executive dysfunction and poor verbal fluency. The patient presented with generally intact memory, mild executive dysfunction, and poor semantic fluency abilities. Given the patient’s high intelligence, he may be more sensitive to cognitive lapses. Neuropsychological results, along with his reported parkinsonian features, are fairly consistent with possible incipient corticobasal degeneration.

Case Report: Callosal disconnection syndrome manifesting as mixed frontal-callosal-posterior alien hand syndrome following extensive corpus callosum infarct

Alien hand syndrome (AHS) is a rare neurological phenomenon first described by Van Vleuten over a century ago. The most widely recognized variants in literature are frontal, callosal, and posterior AHS. AHS due to the corpus callosum lesion can occur alone or as part of callosal disconnection syndrome (CDS). This report presents a unique CDS case manifesting clinical features from all three AHS variants, resulting from an extensive corpus callosum infarct. Our patient exhibited various clinical features from the three AHS variants, which include grasping, groping, and difficulty releasing objects from the hand (anterior); intermanual conflict (callosal); arm levitation, mild hemiparesis, and hemisensory loss (posterior). Additionally, the extensive disruption of the corpus callosal fibers produced neurological manifestations of CDS, such as cognitive impairment, ideomotor and constructional apraxia, behavioral disorder, and transcortical motor aphasia. We employed a range of rehabilitation interventions, such as mirror box therapy, limb restraint strategy, verbal cue training, cognitive behavioral therapy, bimanual hand training, speech and language therapy, and pharmacological treatment with clonazepam. The patient showed almost complete resolution of CDS and AHS features by nine months post-stroke Our case report highlights distinctive clinical variations of AHS and the challenging correlation between clinical manifestations and neuroanatomical substrates. Future studies are necessary to explore the intricate neural connections and the precise function of the corpus callosum. This can be achieved by combining comprehensive neuropsychological testing with diffusion tensor tractography studies. It is also essential to develop a validated tool to standardize AHS assessment. Finally, the scarcity of evidence in rehabilitation interventions necessitates further studies to address the wide knowledge gap in AHS and CDS management.

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.

Progression to corticobasal syndrome: a longitudinal study of patients with nonfluent primary progressive aphasia and primary progressive apraxia of speech.

Nonfluent variant primary progressive aphasia (nfvPPA) and primary progressive apraxia of speech (PPAOS) can be precursors to corticobasal syndrome (CBS). Details on their progression remain unclear. We aimed to examine the clinical and neuroimaging evolution of nfvPPA and PPAOS into CBS. We conducted a retrospective longitudinal study in 140 nfvPPA or PPAOS patients and applied the consensus criteria for possible and probable CBS for every visit, evaluating limb rigidity, akinesia, limb dystonia, myoclonus, ideomotor apraxia, alien limb phenomenon, and nonverbal oral apraxia (NVOA). Given the association of NVOA with AOS, we also modified the CBS criteria by excluding NVOA and assigned every patient to either a progressors or non-progressors group. We evaluated the frequency of every CBS feature by year from disease onset, and assessed gray and white matter volume loss using SPM12. Asymmetric akinesia, NVOA, and limb apraxia were the most common CBS features that developed; while limb dystonia, myoclonus, and alien limb were rare. Eighty-two patients progressed to possible CBS; only four to probable CBS. nfvPPA and PPAOS had a similar proportion of progressors, although nfvPPA progressed to CBS earlier (p-value = 0.046), driven by an early appearance of limb apraxia (p-value = 0.0041). The non-progressors and progressors both showed premotor/motor cortex involvement at baseline, with spread into prefrontal cortex over time. An important proportion of patients with nfvPPA and PPAOS progress to possible CBS, while they rarely develop features of probable CBS even after long follow-up.

Alien hand syndrome: Pathophysiology, semiology and differential diagnosis with psychiatric disorders (Review).

Alien hand syndrome (AHS) is an uncommon neurological condition characterized by involuntary, yet seemingly purposeful, movements of a limb, typically an upper extremity, with variable awareness and control by the affected individual. It is associated with a range of peculiar sensations, such as the feeling of limb estrangement, alien control and involuntary mirroring or restraining of movements. AHS indicates a profound disruption in volitional motor control and personal agency. The aetiology of AHS is the dysfunction of critical brain regions secondary to diverse neurological insults, such as tumours, vascular disorders, infarction or neurodegenerative diseases. It is clinically categorized into the parietal and callosal types, depending on the affected region, with manifestations often linked to the specific brain region affected. The callosal type is particularly challenging to diagnose due to its rarity and potential for nonspecific or concealed symptoms amid concurrent brain injuries. Distinguishing AHS from psychiatric disorders is crucial for accurate diagnosis and improved patient outcomes. Further research is imperative for a deeper understanding of the pathophysiology of AHS and the development of effective treatments. AHS predominantly affects adults and is frequently associated with multiple comorbidities. The syndrome is also exemplified by three distinct motor behaviours: Involuntary grasping, inter-manual conflict and limb levitation accompanied by the sensation of an alien limb or the perception of external control over one's movements. It has a generally good prognosis with partial or total recovery following appropriate rehabilitation techniques, including pharmacological and psychological measures.

Right-sided alien hand in acute parietal infarction: a case report

BackgroundAlien limb is an involuntary movement that is considered a diagnostic feature of corticobasal degeneration syndrome. Few reports describe this condition in acute stroke, and most of them result from right parietal infarction.Case presentationThis is a case of acute stroke presenting with a right-sided alien limb that was followed by right-sided weakness and aphasia. Effective management of the stroke was achieved through intravenous thrombolysis with the resolution of most symptoms except for a right-side sensory deficit. Magnetic resonance imaging of the brain showed acute parietal infarction involving the left sensory cortex.ConclusionsAlthough very rare, right-sided alien limb can occur due left parietal infarction.

Alien Hand Syndrome: A Case Report Decoding the Enigmatic Limb

Alien Hand Syndrome (AHS) is a rare condition characterised by involuntary hand movements occurring without the patient’s intention. While AHS has various causes, it is frequently associated with ischemic stroke, post-corpus callosotomy, degenerative conditions, and has more recently been observed in cortico-basal degeneration. This case report highlights a 62-year-old male patient experiencing involuntary movement in his right hand three days after admission with an ischemic stroke involving the left fronto-parietal lobe and corpus callosum. The predominant symptoms included compulsive groping, inter-manual conflict, and hemi-anaesthesia in his right hand. The callosal subtype arises from corpus callosum damage and often involves inter-manual conflict. However, callosal infarction is uncommon due to the abundant blood supply. This case report describes a case of AHS caused by callosal infarction, confirmed through magnetic resonance imaging, specifically showing infarction in the left corpus callosum. The patient exhibited symptoms consistent with the anterior variant based on radiographic findings. However, features of the posterior variant were also observed.

Diferenças fenotípicas e do PET FDG na síndrome corticobasal: comparação de dois casos

ABSTRACT Corticobasal syndrome (CBS) is a rare cause of dementia and comprises varied combinations of subcortical signs (akinetic-rigid parkinsonism, dystonia, or myoclonus) with cortical signs (apraxia, alien hand or cortical sensory deficit), usually asymmetric. We aimed to report and compare the clinical and neuroimaging presentation of two patients diagnosed with CBS. While case 1 had severe non-fluent aphasia associated with mild apraxia and limb rigidity, case 2 had a more posterior cognitive impairment, with a different language pattern associated with marked visuospatial errors and hemineglect. FDG PET played a significant role in diagnosis, suggesting, in the first case, corticobasal degeneration and, in the second, Alzheimer's disease pattern. CBS has been widely studied with the advent of new in vivo methods such as brain FDG PET. Studies that deepen the phenotypic and biomarker heterogeneity of CBS will be of great importance for better classification, prognosis, and treatment of the condition.

Creutzfeldt-Jakob Disease Presenting with Alien Hand.

Creutzfeldt-Jakob Disease Presenting with Alien Hand.

Cytotoxic Lesion of the Corpus Callosum: A Case of Metabolic Disease in a New Mother

Cytotoxic lesions of the corpus callosum (CLOCCs) represent an array of different conditions involving the corpus callosum. CLOCCs do not demonstrate definite signs or symptoms of hemispheric disconnection, such as alien hand syndrome, pseudo-neglect, apraxia of the left hand, agraphia, alexia, and visual apraxia. In fact, symptoms are generally related to the primary cause of the cytotoxic lesion, such as pharmaceutical agents, malignancies, infections, metabolic disorders, trauma, and others.

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.

Alien hand syndrome, a rare presentation of corpus callosum and cingulate infarction

Alien hand syndrome (AHS) is a rare apraxia syndrome, characterized by involuntary and uncontrollable movements of one upper limb, often accompanied by intermanual conflict. Damage to the corpus callosum, acute infarction and neurodegenerative disease may result in AHS. Based on the presentation and impairment region, AHS has three variants: frontal, callosal and posterior. Each type may have a different clinical presentation. A total of 157 patients admitted to hospital with corpus callosum infarction between 2012 and 2022 were included for this study, of whom a number of 5 presented with AHS. 4 of them had significant symptoms of intermanual conflict and 1 had strong grip symptoms in the affected upper limb. Moreover, new infarcts involving the corpus callosum and cingulate gyrus were found on MRI in all five patients. We simultaneously performed a retrospective study on all reported AHS cases caused by infarction of the corpus callosum. Case reports and literature reviews were conducted in order to provide clinicians with a better understanding of AHS, its etiology, clinical presentation, diagnosis, and treatment.

The Girl Who Wants to Get Rid of Her Left Leg—Body Identity Dysphoria

Introduction: One of the strangest kinds of misperceptions of the body is “Body Integrity Dysphoria” (BID), formerly named as “Body Identity Integrity Disorder” (BIID). The affected people have the feeling that a limb is not part of their body. They can feel it, they can use it, they can move it, but they cannot get along with the fact that it is a part of their own body. Most feel the need for an amputation of a leg, others of both legs, some want a palsy and use a wheelchair. Still discussed is whether other disablements such as blindness, dumbness, deafness or a desire to have an incontinency can be included in this diagnosis. This review discusses parallels and differences to transgender/trans identity, body dysmorphic disorder, alien limb syndrome, hemineglect, and self-induced amputations in schizophrenic patients. The cause for the need to be disabled is still unknown; the review gives an overview about psychological and neurological theories of explanation and what kind of therapy may help. Methods: This is a narrative review of about 20 years of research about Body Integrity Dysphoria by the author. Results: Overall, no psychopathological deviations were found, none of the affected persons examined by us were actually delusional or schizophrenic, which underlines that there is a neurological malfunction in the brain that has existed since birth. However, psychological mechanisms intensify the symptoms. There are clear parallels to other forms of interference between the external body and mental body representation. Different types of therapies have been able to provide help to better deal with BID, but there has been little to bring about a real cure. In contrast, BID-affected persons who achieved amputation (or other desired forms of disability) were satisfied and able to return to work. Conclusions: BID remains an enigmatic disorder. We have learned a lot over the past 20 years that the mental and physical bodies do not have to match.

Scrambler Therapy for the Treatment of Pain and Sensory Symptoms in Corticobasal Syndrome: A Case Series

BACKGROUND: Corticobasal syndrome (CBS) is a rare atypical parkinsonian disorder. Pain occurs in one-third of patients; current pain treatment options are often inadequate. Scrambler therapy (ST) is a noninvasive cutaneous method of neuromodulation that has shown success in other refractory neuropathic pain syndromes. CASE REPORT: We treated 3 patients with CBS with one to 3 40-minute sessions of ST, capturing the terminal arborization of the peripheral nerves within the affected painful dermatomes. All patients reported rapid and complete relief of their pain, with one patient having 4 months of ongoing relief, along with complete resolution of alien limb phenomenon. Another patient experienced 11 months of relief, with resumption of pain relief with retreatment after symptoms gradually returned. None have experienced complications or adverse effects to date. CONCLUSION: ST may represent a new noninvasive treatment for central pain associated with CBS. Further studies with longer follow-ups are warranted. KEY WORDS: Scrambler therapy, atypical parkinsonism, corticobasal syndrome, chronic pain, central pain

Predictors of Survival in Atypical Parkinsonian Syndromes in a Tunisian Cohort (P8-11.006)

<h3>Objective:</h3> Our aim was to investigate demographic, clinical and genetic survival factors in a Tunisian cohort with atypical parkinsonian syndromes (APS). <h3>Background:</h3> APS encompass a spectrum of neurodegenerative diseases including dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS), all characterized by faster progression and earlier mortality compared to Parkinson’s disease. However, the predictors of survival are still controversial. <h3>Design/Methods:</h3> We conducted a retrospective study over a period of 19 years (2003–2021) in the Department of Neurology of Razi University Hospital, in Tunis, Tunisia, including patients diagnosed with APS. Survival was explored using Kaplan-Meier analysis. Demographic, clinical, neuropsychological features and frequency of Apolipoprotein Epsilon 4 (ApoEɛ4) allele were analyzed in the survival analysis. <h3>Results:</h3> We included 340 APS patients (151 DLB, 74 PSP, 70 MSA, 45 CBS). Median survival was 6 years from disease onset in DLB and MSA and 7 years in PSP and CBS. It was significantly shorter for men (p=0.005) and for patients with memory symptoms at onset (p=0.040) in DLB, later age of onset (&gt;65 years, p=0.021), earlier dysphagia and ApoEɛ4 allele carrying status in PSP patients. In MSA, median survival was shorter in parkinsonian subtype (MSA-P) compared to cerebellar subtype (MSA-C) in patients having urinary dysfunction. Although the presence of stridor was associated with shorter survival (6 vs 9 years), the difference was not statistically significant (p=0.090). In CBS, the presence of alien limb syndrome (p=0.031), dementia (p=0.026) and tremor-dominant parkinsonian syndrome (p=0.019) were associated with shorter survival. <h3>Conclusions:</h3> Our results showed shorter survival in synucleinopathies compared to tauopathies with different predictive demographic and clinical factors across APS. ApoEɛ4 seemed to have an effect only in PSP. Larger prospective studies are needed to better investigate the various survival determinants. <b>Disclosure:</b> Dr. Nasri has nothing to disclose. Ikram Sghaier has nothing to disclose. Mrabet Saloua has nothing to disclose. Mr. Abida has nothing to disclose. Alya GHARBI has nothing to disclose. Amira Souissi has nothing to disclose. Mouna BenDjebara has nothing to disclose. Amina Gargouri has nothing to disclose. Dr. Kacem has nothing to disclose. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Gouider has received research support from Clinical Investigation Center. The institution of Dr. Gouider has received research support from Menactrims.

A case of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia presenting with alien hand syndrome.

A case of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia presenting with alien hand syndrome.

18F]PM-PBB3-PET Reveals Clinical and [18F]FDG-PET Mimics of 4-Repeat Tauopathy Caused by Creutzfeld-Jakob Disease.

This image depicts [18F] FDG and [18F]PM-PBB3 uptake surface projections of two male patients with complex movement disturbances. They were referred for PET imaging with the suspected diagnosis of a 4-repeat (4R)-tauopathy Figure 1. Patient #1 (79 years) presented with an aggressive, non-levodopa responsive hypokinetic-rigid syndrome with early falls and a vertical supranuclear gaze palsy. Patient #2 (68 years) presented with unusually rapidly progressive dystonia, right-sided rigor, bradykinesia, alien limb phenomenon and action myoclonus of the right arm, likewise without response to levodopa. Disease duration was 11 and 5 months, respectively. CSF levels of tau and amyloid in either patient were not indicative for Alzheimer's disease. In both, [18F] FDG-PET revealed a corticobasal degeneration-like bilateral reduction of cerebral glucose metabolism in frontoparietal cortical areas (arrowheads) and in the thalamus.1 A clear asymmetry to the detriment of the right hemisphere was observed in #1, whereas hypometabolism of the left hemisphere was only slightly pronounced in #2. Subsequent imaging with tau ligand [18F]PM-PBB32 showed elevated binding (arrowheads, asterisks indicate unspecific uptake of the choroid plexus) suggestive for pathological tau aggregates in frontal and parietal areas of #1, supporting the diagnosis of a 4R-tauopathy.2 In contrast, the lack of specific [18F]PM-PBB3 binding in patient #2 questioned the diagnosis of a 4R-tau related corticobasal syndrome (CBS; eg, progressive supranuclear palsy—CBS). Diagnosis of Creutzfeld-Jakob disease in this patient was made via 14–3-3 and PrPSc aggregation assays. In conclusion, [18F]PM-PBB3-PET reveals clinical and [18F] FDG-PET mimics of 4R-tau CBS caused by Creutzfeld-Jakob disease. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical analysis: A. Design, B. Execution, C. Review and critique; (3) Manuscript: A. Writing of the first draft, B. Review and critique. N.S.: 1A, B, 1C, 2C, 3A. G.B.: 1C, 2B, 2C, 3B. P.T.M.: 1B, 2A, 2C, 3B. M.R.: 1B, 2C, 3B. J.B.: 1C, 2A, 2C, 3A. Materials required for the synthesis of [18F] APN-1607 were generously provided by Aprinoia Therapeutics Limited. Open Access funding enabled and organized by Projekt DEAL. Ethical Compliance Statement: The authors confirm that the approval of an institutional review board was not required for this work. Both patients gave written informed consent for the scientific use of imaging and clinical data. Funding Sources and Conflicts of Interest: Nils Schröter, Berta-Ottenstein-Programme for Clinician Scientists, Faculty of Medicine, University of Freiburg. The authors have no potential conflict of interest to report. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Financial Disclosures for the Previous 12 Months: The authors have nothing to disclose.

Rare forms of dementia-Atypical variants of Alzheimer's dementia

In Germany, around 1.8million people currently suffer from dementia and the numbers are increasing. The main cause of dementia is Alzheimer's disease. This is classically manifested in the form of an amnestic syndrome but also encompasses various atypical variants, especially in younger patients and in the clinical routine are not always easy to recognize. These are described in this narrative review with case studies. Posterior cortical atrophy (PCA) presents with visual disorders, in the logopenic variants of primary progressive aphasia (lvPPA) impaired word retrieval is the main symptom, in the frontal variant of Alzheimer's disease behavioral disorders are prominent and in corticobasal syndrome (CBS) an akinetic rigid Parkinson's syndrome with alien limb phenomenon. As the clinical presentation of these atypical variants shows an overlap with other dementia disorders, the differential diagnosis is often challenging. In this context amyloid biomarkers can provide valuable services.

A Patient with Corticobasal Syndrome and Progressive Non-Fluent Aphasia (CBS-PNFA), with Variants in ATP7B, SETX, SORL1, and FOXP1 Genes.

Our aim was to analyze the phenotypic-genetic correlations in a patient diagnosed with early onset corticobasal syndrome with progressive non-fluent aphasia (CBS-PNFA), characterized by predominant apraxia of speech, accompanied by prominent right-sided upper-limb limb-kinetic apraxia, alien limb phenomenon, synkinesis, myoclonus, mild cortical sensory loss, and right-sided hemispatial neglect. Whole-exome sequencing (WES) identified rare single heterozygous variants in ATP7B (c.3207C&gt;A), SORL1 (c.352G&gt;A), SETX (c.2385_2387delAAA), and FOXP1 (c.1762G&gt;A) genes. The functional analysis revealed that the deletion in the SETX gene changed the splicing pattern, which was accompanied by lower SETX mRNA levels in the patient's fibroblasts, suggesting loss-of-function as the underlying mechanism. In addition, the patient's fibroblasts demonstrated altered mitochondrial architecture with decreased connectivity, compared to the control individuals. This is the first association of the CBS-PNFA phenotype with the most common ATP7B pathogenic variant p.H1069Q, previously linked to Wilson's disease, and early onset Parkinson's disease. This study expands the complex clinical spectrum related to variants in well-known disease genes, such as ATP7B, SORL1, SETX, and FOXP1, corroborating the hypothesis of oligogenic inheritance. To date, the FOXP1 gene has been linked exclusively to neurodevelopmental speech disorders, while our study highlights its possible relevance for adult-onset progressive apraxia of speech, which guarantees further study.