Vertical Gaze Research Articles

Spectrum of Movement Disorders of Late-Onset Niemann-Pick Disease Type C

Niemann-Pick disease type C (NPC), is a rare lysosomal storage disorder, which has a variable presentation based on the age of onset. We describe five adult/adolescent-onset NPC cases presenting with a range of movement disorders along with vertical supranuclear gaze palsy as part of the clinical presentation. A diagnostic delay of 4-17 years from the symptom onset was found in this case series. A high index of clinical suspicion in adult/adolescent patients presenting with vertical supranuclear gaze palsy along with various movement disorder phenomenology can help in the early diagnosis of NPC.

Clinical Correlation Between Vertical Gaze Palsy and Midbrain Volume in Progressive Supranuclear Palsy.

Supranuclear vertical gaze palsies and slowed vertical saccades are characteristic clinic features of progressive supranuclear palsy (PSP). The "hummingbird sign," reflective of midbrain atrophy, is a classic radiographic sign of PSP. Correlation between eye movement abnormalities and radiographic findings in PSP has been reported previously. However, due to the use of clinical criteria not commonly employed in neuro-ophthalmic practice and neuroimaging techniques that are not widely available, it remains unclear whether correlation between midbrain structure and characteristic ocular-motor disturbances can be helpful to neuro-ophthalmologists seeking to adjudicate difficult or unusual diagnostic cases. Patients with a diagnosis of probable PSP according to Movement Disorders Society criteria were studied retrospectively. A neuroradiologist calculated brainstem volumes in enrolled participants and normal controls. Spearman correlations were used to correlate the extent of eye movement limitation as assessed by 2 neuro-ophthalmologists with brainstem volumes. Fourteen participants with PSP and 15 healthy controls with similar age and gender distribution were enrolled and evaluated retrospectively. All 14 participants with PSP had undergone MRIs. Midbrain atrophy significantly correlated with the PSP rating scale (P < 0.001). PSP patients had significantly reduced volumes in the midbrain (P -0.0026), tegmentum (0.0001), tectum (0.0001), and medulla (P = 0.0024) compared with normal controls. Notes documenting quantified ocular motor function were available in 7 of 14 participants with PSP. Midbrain atrophy significantly correlated with in the extent of upward gaze limitation (P = 0.03). The severity of upward gaze limitation correlates with the severity of midbrain atrophy in patients with PSP. Recognition of this correlation may help to adjudicate diagnostic dilemmas and guide further evaluation.

Locked-In Syndrome: A Systematic Review of Long-Term Management and Prognosis.

Locked-in syndrome (LIS) is a neurological disorder in which there is damage to the ventral pons and caudal midbrain. An ischemic cause, such as basilar artery occlusion, can often lead to LIS. LIS has three subtypes: classical, partial, and total. There is loss of motion in the four extremities in classical LIS, loss of horizontal gaze, and aphasia. In partial LIS, the patient still has some motor function. Complete LIS has the worst outcome because patients cannot blink or have vertical gaze, thus rendering them incapable of communicating. Most cases of LIS occur due to ischemic infarcts. These patients require a great deal of physical rehabilitation to regain partial motor ability and a means to communicate. While the clinical features and pathophysiology are known, the prognosis and long-term treatment remain unknown.We conducted a systematic review using the Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) protocol. We use an advanced PubMed strategy using the inclusion criteria of observational studies or clinical trials conducted in the last 20 years, written in English, and conducted on humans. We excluded systematic reviews, literature reviews, metanalysis, and studies that did not meet the outcomes of our objectives.The prognosis of LIS is not good, and most patients remain locked in, with poor quality of life, especially motor functions. Respiratory failure and depression are big comorbidities. In the acute setting, patients benefit from rapid intervention. The subacute treatment needs to manage aggressively to improve functional scores best. The long-term treatment focus is on the quality of life and managing comorbidities.

Occipital posterior interhemispheric supratentorial approach for resection of midbrain cavernous malformation.

Approaches to the pineal region are various, and each has its advantages and disadvantages. The authors present a case of a 50-year-old woman who presented with progressive hemiparesis and vertical gaze palsy; she was diagnosed with a midbrain cavernous malformation. The patient underwent an occipital posterior interhemispheric supratentorial transpineal approach with gross-total resection. On long-term follow-up, her symptoms significantly improved. The authors review the regional anatomy and present the operative video. They also discuss the various approaches with their indications, advantages, and disadvantages.The video can be found here: https://stream.cadmore.media/r10.3171/2021.4.FOCVID2133.

Visio-Vestibular Deficits in Healthy Child and Adolescent Athletes.

To determine the relationship between patient characteristics and performance on the visio-vestibular examination (VVE) in a cohort of healthy youth athletes and explore the potential association between the VVE and other standardized concussion batteries. Cross-sectional. Suburban middle and high school. One hundred ninety subjects age 11 to 18 enrolled before their respective scholastic sport season between August 2017 and March 2020. Patient age, sex, concussion history, comorbidities, hours of weekly exercise, Sport Concussion Assessment Tool, 5th edition (SCAT-5), King-Devick (K-D), Postconcussion Symptom Inventory (PCSI). Visio-vestibular examination abnormalities (smooth pursuit, horizontal and vertical saccades, horizontal and vertical gaze stability, convergence, right and left monocular accommodation, complex tandem gait). Overall, 29.5% of subjects had at least one of 9 VVE elements abnormal, 7.9% at least 2, and 3.2% at least 3. None of 72 comparisons of the VVE elements, when stratified by age, sex, concussion history, history of headaches, attention deficit hyperactivity disorder, learning issues, psychiatric problems, motion sickness, or weekly hours of exercise, reached significance using the Benjamini-Hochberg procedure at a false discovery rate of 5%. There were no significant associations between VVE elements and the SCAT-5, K-D, or PCSI. The VVE is robust across multiple patient characteristics. Although healthy subjects may have one abnormal element, multiple abnormal elements are a less common feature, making multiple abnormal elements more indicative of concussion, highlighting the use of this assessment in the setting of injury. The VVE tests unique domains when compared with the PCSI, SCAT-5, and K-D.

Vertical saccadic palsy and foveal retinal thinning in Niemann-Pick disease type C.

IntroductionNiemann-Pick type C (NPC) is a lysosomal storage disease that is progressive and life-limiting, with an estimated incidence of 1:120,000 live births. In addition to systemic manifestation with (hepato-)splenomegaly, there are a number of neurological manifestations (ataxia, dysarthria, dementia, cataplexy, epileptic seizures, and psychiatric disorders). Characteristic is vertical supranuclear gaze palsy, which is often overlooked. Early diagnosis and start of therapy improve quality of life. This study aimed to characterize oculomotor dysfunction of NPC patients, and to provide ophthalmologic data including retinal imaging.MethodsEighteen patients with biochemically or genetically diagnosed NPC completed oculomotor and ophthalmologic examination. Ten of them performed saccadometry by infrared based video-oculography. Saccadic parameters were compared to 100 healthy controls, and were correlated with clinical variables. Another subgroup of eight patients received optical coherence tomography (OCT) of the optic disc and the macula, of which the segmented layers were analysed using a crude linear mixed model, and one adjusted for age, sex, and spherical equivalent.ResultsSaccadometry revealed slowed peak velocity compared to controls most evident vertically. Peak velocity correlated negatively with SARA-Score, but correlation with clinical assessment of saccades was not significant. Clinical features in the assessment of vertical saccades were intensive blinking and head movements to initiate gaze changes, and lateral trajectory of the eyes. Macular OCT revealed significant total retinal thinning in the fovea, specifically of the outer nuclear layer and outer retinal layer. Para- and perifoveal retinal thicknesses, as well as peripapillary retinal nerve fibre layer were normal.ConclusionsFoveal thinning was revealed in NPC. It remains to be shown, whether OCT will prove to be useful to monitor progression. Saccadic impairment reflects CNS involvement and therefore is a parameter to demonstrate the progression of NPC, and potentially also the efficacy of new therapies. Saccadometry, in contrast to clinical investigation, allows the precise evaluation of saccades.

Environmental Risk Factors for Progressive Supranuclear Palsy.

Typically, progressive supranuclear palsy (PSP) is clinically characterized by slow vertical saccades or supranuclear gaze palsy, levodopa-resistant parkinsonism with predominant axial symptoms, and cognitive executive impairment. Over the past decades, various PSP phenotypes, including PSP with predominant parkinsonism, PSP with corticobasal syndrome, PSP with progressive gait freezing, and PSP with predominant frontal dysfunction, have been identified from pathologically confirmed cases. Expanding knowledge led to new diagnostic criteria for PSP that with increased disease awareness led to increased PSP prevalence estimates. The identification of environmental and modifiable risk factors creates an opportunity to intervene and delay the onset of PSP or slow disease progression. To date, despite the increasing number of publications assessing risk factors for PSP, few articles have focused on environmental and lifestyle risk factors for this disorder. In this article, we reviewed the literature investigating the relationship between PSP and several environmental and other modifiable lifestyle risk factors. In our review, we found that exposures to toxins related to diet, metals, well water, and hypertension were associated with increased PSP risk. In contrast, higher education and statins may be protective. Further case-control studies are encouraged to determine the exact role of these factors in the etiopathogenesis of PSP, which in turn would inform strategies to prevent and reduce the burden of PSP.

Gaze During Locomotion in Virtual Reality and the Real World.

How vision guides gaze in realistic settings has been researched for decades. Human gaze behavior is typically measured in laboratory settings that are well controlled but feature-reduced and movement-constrained, in sharp contrast to real-life gaze control that combines eye, head, and body movements. Previous real-world research has shown environmental factors such as terrain difficulty to affect gaze; however, real-world settings are difficult to control or replicate. Virtual reality (VR) offers the experimental control of a laboratory, yet approximates freedom and visual complexity of the real world (RW). We measured gaze data in 8 healthy young adults during walking in the RW and simulated locomotion in VR. Participants walked along a pre-defined path inside an office building, which included different terrains such as long corridors and flights of stairs. In VR, participants followed the same path in a detailed virtual reconstruction of the building. We devised a novel hybrid control strategy for movement in VR: participants did not actually translate: forward movements were controlled by a hand-held device, rotational movements were executed physically and transferred to the VR. We found significant effects of terrain type (flat corridor, staircase up, and staircase down) on gaze direction, on the spatial spread of gaze direction, and on the angular distribution of gaze-direction changes. The factor world (RW and VR) affected the angular distribution of gaze-direction changes, saccade frequency, and head-centered vertical gaze direction. The latter effect vanished when referencing gaze to a world-fixed coordinate system, and was likely due to specifics of headset placement, which cannot confound any other analyzed measure. Importantly, we did not observe a significant interaction between the factors world and terrain for any of the tested measures. This indicates that differences between terrain types are not modulated by the world. The overall dwell time on navigational markers did not differ between worlds. The similar dependence of gaze behavior on terrain in the RW and in VR indicates that our VR captures real-world constraints remarkably well. High-fidelity VR combined with naturalistic movement control therefore has the potential to narrow the gap between the experimental control of a lab and ecologically valid settings.

Small Pontine Tegmental Infarct Presenting as Ipsilateral Sixth and Seventh Nerve Palsies, Ipsilateral INO and Vertical Gaze Restriction (2500)

Small Pontine Tegmental Infarct Presenting as Ipsilateral Sixth and Seventh Nerve Palsies, Ipsilateral INO and Vertical Gaze Restriction (2500)

Autosomal recessive spinocerebellar ataxia SCAR8/ARCA1: first families detected in Spain

IntroductionAutosomal recessive spinocerebellar ataxia type 8 (ARCA1/SCAR8) is caused by mutations of the SYNE1 gene. The disease was initially described in families from Quebec (Canada) with a phenotype of pure cerebellar syndrome, but in recent years has been reported with a more variable clinical phenotype in other countries. Cases have recently been described of muscular dystrophy, arthrogryposis, and cardiomyopathy due to SYNE1 mutations. ObjectiveTo describe clinical and molecular findings from 4 patients (3 men and one woman) diagnosed with ARCA1/SCAR8 from 3 Spanish families from different regions. Material and methodsWe describe the clinical, paraclinical, and genetic results from 4 patients diagnosed with ARCA1/SCAR8 at different Spanish neurology departments. ResultsOnset occurred in the third or fourth decade of life in all patients. After 15 years of progression, 3 patients presented pure cerebellar syndrome, similar to the Canadian patients; the fourth patient, with over 30 years’ progression, presented vertical gaze palsy, pyramidal signs, and moderate cognitive impairment. In all patients, MRI studies showed cerebellar atrophy. The genetic study revealed distinct pathogenic SYNE1 mutations in each family. ConclusionsARCA1/SCAR8 can be found worldwide and may be caused by many distinct mutations in the SYNE1 gene. The disease may manifest with a complex phenotype of varying severity.

Assessment of Saccades and Gaze Stability in the Diagnosis of Pediatric Concussion.

To evaluate the discriminatory ability of different repetition increments of saccades and gaze stability testing for diagnosing concussion in adolescents. Cross-sectional. Suburban high school and academic pediatric tertiary care center. Sixty-nine adolescent athletes within 28 days of a sports- or recreation-related concussion and 69 adolescent athletes without recent concussion. Symptom provocation with horizontal and vertical saccades and gaze stability testing performed up to 30 repetitions. Sensitivity and specificity at 10-repetition increments (≤10, ≤20, ≤30) and area under the receiver operating characteristic curves (AUC) of a visio-vestibular examination (VVE) subscore, scored 0 to 4 based on the number of assessments with symptom provocation, at each repetition increment. Sensitivity improved when increasing from ≤10 to ≤20 to ≤30 repetitions for horizontal (25% to 50% to 69%) and vertical (32% to 52% to 74%) saccades and horizontal (19% to 45% to 71%) and vertical (23% to 45% to 72%) gaze stability. Specificity was comparable at ≤10 and ≤20 repetitions, but decreased at ≤30 repetitions across assessments. For a VVE subscore (0-4) based on the number of symptomatic assessments, the discriminatory ability of the test was highest at ≤20 repetitions (AUC of 0.79) with an optimal subscore of one (sensitivity 59%, specificity 96%). A VVE including a higher threshold level of repetitions for saccades and gaze stability has improved discriminatory ability for concussion, with an optimized AUC of 0.79 at ≤20 repetitions. The findings in this study suggest that a higher threshold level of repetitions of 2 commonly used visio-vestibular assessments enables clinicians to more accurately diagnose youth concussion.

Midbrain atrophy related to parkinsonism in a non-coding repeat expansion disorder: five cases of spinocerebellar ataxia type 31 with nigrostriatal dopaminergic dysfunction

BackgroundSpinocerebellar ataxia type 31 (SCA31) is caused by non-coding pentanucleotide repeat expansions in the BEAN1 gene. Clinically, SCA31 is characterized by late adult-onset, pure cerebellar ataxia. To explore the association between parkinsonism and SCA31, five patients with SCA31 with concomitant nigrostriatal dopaminergic dysfunction (NSDD) development, including three cases of L-DOPA responsive parkinsonism, were analyzed.MethodsTo assess regional brain atrophy, cross-sectional and longitudinal imaging analyses were retrospectively performed using magnetic resonance imaging (MRI) planimetry. The midbrain-to-pons (M/P) area ratio and cerebellar area were measured on midsagittal T1-weighted MRI in five patients with SCA31 with concomitant NSDD (NSDD(+)), 14 patients with SCA31 without NSDD (NSDD(−)), 32 patients with Parkinson’s disease (PD), and 15 patients with progressive supranuclear palsy (PSP). Longitudinal changes in the M/P area ratio were assessed by serial MRI of NSDD(+) (n = 5) and NSDD(−) (n = 9).ResultsThe clinical characteristics assessed in the five patients with NSDD were as follows: the mean age at NSDD onset (72.0 ± 10.8 years), prominence of bradykinesia/akinesia (5/5), rigidity (4/5), tremor (2/5), dysautonomia (0/5), vertical gaze limitation (1/5), and abnormalities on 123I-ioflupane dopamine transporter scintigraphy (3/3) and 3-Tesla neuromelanin MRI (4/4). A clear reduction in the midbrain area and the M/P area ratio was observed in the NSDD(+) group (p < 0.05) while there was no significant difference in disease duration or in the pons area among the NSDD(+), NSDD(−), and PD groups. There was also a significant difference in the midbrain and pons area between NSDD(+) and PSP (p < 0.05). Thus, mild but significant midbrain atrophy was observed in NSDD(+). A faster rate of decline in the midbrain area and the M/P area ratio was evident in NSDD(+) (p < 0.05).ConclusionThe clinical characteristics of the five patients with SCA31 with concomitant NSDD, together with the topographical pattern of atrophy, were inconsistent with PD, PSP, and multiple system atrophy, suggesting that SCA31 may manifest NSDD in association with the pathomechanisms underlying SCA31.

Dream Enactment Behavior Disorder Associated with Pallido-Nigro-Luysian Degeneration and Tau Proteinopathy.

Pallido-nigro-luysian atrophy (PNLA) is a rare neurodegenerative disorder with only a few cases reported to date. Although the clinical picture usually resembles progressive supranuclear palsy, pathological examination reveals more selective atrophy and loss of neurons in the globus pallidus, substantia nigra and subthalamic nucleus. To describe the clinical features and pathological findings of a patient with PNLA. Case report with clinico-pathological discussion. An 83-year-old man presented to our clinic with a vertical supranuclear gaze palsy, parkinsonism, gait impairment and sleep abnormalities suggestive of REM-sleep behavior disorder. Neuropathological examination 5 years after symptom onset revealed subcortical tau proteinopathy compatible with a PNLA pattern. There was also an associated mild degree of limbic/subcortical inflammatory response, Alzheimer's disease-related changes, as well as argyrophilic grain disease. We present a comprehensive clinico-pathological discussion of a patient with PNLA. Besides parkinsonism and vertical supranuclear gaze palsy, the patient also had a sleep disorder, clinically suggestive of REM behavioral disorder, which has not been previously reported in PNLA. We expand the clinical phenotype of this rare condition and provide neuropathological evidence for the associated abnormalities.

Genotype-Phenotype Relations for the Atypical Parkinsonism Genes: MDSGene Systematic Review.

This Movement Disorder Society Genetic mutation database Systematic Review focuses on monogenic atypical parkinsonism with mutations in the ATP13A2, DCTN1, DNAJC6, FBXO7, SYNJ1, and VPS13C genes. We screened 673 citations and extracted genotypic and phenotypic data for 140 patients (73 families) from 77 publications. In an exploratory fashion, we applied an automated classification procedure via an ensemble of bootstrap-aggregated (“bagged”) decision trees to distinguish these 6 forms of monogenic atypical parkinsonism and found a high accuracy of 86.5% (95% CI, 86.3%–86.7%) based on the following 10 clinical variables: age at onset, spasticity and pyramidal signs, hypoventilation, decreased body weight, minimyoclonus, vertical gaze palsy, autonomic symptoms, other nonmotor symptoms, levodopa response quantification, and cognitive decline. Comparing monogenic atypical with monogenic typical parkinsonism using 2063 data sets from Movement Disorder Society Genetic mutation database on patients with SNCA, LRRK2, VPS35, Parkin, PINK1, and DJ-1 mutations, the age at onset was earlier in monogenic atypical parkinsonism (24 vs 40 years; P = 1.2647 × 10−12) and levodopa response less favorable than in patients with monogenic typical presentations (49% vs 93%). In addition, we compared monogenic to nonmonogenic atypical parkinsonism using data from 362 patients with progressive supranuclear gaze palsy, corticobasal degeneration, multiple system atrophy, or frontotemporal lobar degeneration. Although these conditions share many clinical features with the monogenic atypical forms, they can typically be distinguished based on their later median age at onset (64 years; IQR, 57–70 years). In conclusion, age at onset, presence of specific signs, and degree of levodopa response inform differential diagnostic considerations and genetic testing indications in atypical forms of parkinsonism.

Improvement in mild anti-IgLON5 encephalopathy without immunotherapy: a case report

BackgroundAnti-IgLON5 antibody-related encephalopathy is a recently discovered and rare autoimmune disease, and its diagnosis and treatment are more challenging than for other autoimmune encephalopathic diseases. Sleep disorder is the most prominent symptom of the disease. It can also present with gait instability, dysarthria, dysphagia, dementia, ataxia, autonomic nervous system dysfunction, chorea, vertical gaze paralysis, and other symptoms. Immunotherapy remains the primary treatment for this disease; however, there is no definitive conclusion regarding the effect of immunotherapy. The clinical symptoms of the reported cases of anti-IgLON5 antibody-related encephalopathy were generally severe. However, the symptoms in our patient were mild and relieved without immunotherapy, unlike the previously reported cases.Case presentationA 62-year-old man presented with behavioural abnormalities and involuntary movements after nearly 2 months of fever and headache. He also had symptoms of mild sleep disorder. Due to the abnormal levels of infection-related indicators, antiviral treatment was started on the day of admission. The serum analysis confirmed the presence of IgLON5 antibody, and the patient was found to be genetically susceptible. The patient’s symptoms resolved rapidly without immunotherapy and did not recur.ConclusionsThis case demonstrated that IgLON5 antibody-related encephalopathy might have mild manifestations. Infection and a genetic predisposition may be important causes for the disease. Patients with a mild disease may have a better prognosis.

Chronic Lithium Neurotoxicity Presenting as Dementia: A Case Report

<h3>Introduction</h3> Treatment with Lithium can be associated with a continuum of neurological side effects, ranging from benign tremors to early reversible lithium neurotoxicity, to chronic irreversible lithium neurotoxicity. Among chronic systemic adverse effects of Lithium, neurotoxicity has been reported to be the most common, followed by renal and cardiovascular toxicity (Sunn et al). Data on lithium toxicity in the elderly is limited but available data indicates that adverse effects occur more commonly in the context of chronic therapeutic administration of lithium rather than instances of overdose (Oakly et al). EEG and nerve conduction studies show notable changes that correlate with the increased duration of Li therapy (Fountoulakis et al). Older adults are more susceptible to side effects even with "normal" lithium levels for reasons such as declined renal function, reduced volume of distribution, medical comorbidities, concomitant medications, and drug interactions. Here we present a case of an elderly man with chronic lithium neurotoxicity associated with significant cognitive changes and severe disability. This will be followed by a review of literature of chronic lithium neurotoxicity in the geriatric population. <h3>Methods</h3> Case of Mr. A: We present the case of a 72 year old man who presented to the Memory Clinic with a diagnosis of Alzheimer's disease (AD) since the age of 55. His presentation was also notable for progressive aphasia and he had a PEG tube placed for feeding. His cognitive deficits were most significant in the domains of executive and visuospatial functioning, memory, and language. Physical exam findings were notable for mild left hand tremor, difficulties with balance, slow gait with short steps and a decreased arm swing, limited vertical gaze, and dysphagia. He was independent with his ADLs but dependent on IADLs due to aforementioned cognitive and physical findings. Other psychiatric diagnoses included Bipolar Disorder, Substance Use Disorder in remission. At the time of his evaluation, Mr. A had been on Lithium for over 20 years with records for the past three years showing therapeutic levels .5-1.1mmol/L. Although the patient had been previously diagnosed with AD, his relatively stable neuropsychological profile over the last 15 years called the diagnosis of AD into question and this was confirmed by negative amyloid imaging. The patient had yearly therapeutic levels of Lithium until his wife's concern for further insidious cognitive decline in the domains of language and memory, along with worsening gait and tremor prompted checking a Lithium level which was 1.8. Patient was subsequently weaned off Lithium over several months. At the time of this writing this abstract, Mr. A's cognition and motor function are significantly improving, to the extent of no longer requiring PEG for dysphagia. Electronic searches of The Cochrane Central Register of Controlled Trials and the standard bibliographic databases PubMed, MEDLINE, EMBASE, and PsycINFO will be performed for papers focusing on chronic lithium neurotoxicity in older adults. Keywords include "lithium" and "adverse effects" or neurotoxicity" or "neurological manifestations." Original research, case reports, and reviews will be included. Data focusing on older adults will be extracted and presented. <h3>Results</h3> Initial search for literature focusing on chronic lithium neurotoxicity yielded 4 papers. Data from these papers will be extracted. The range of neurological adverse effects, both physical and mental, will be described. This will be followed by a discussion of risk and precipitating factors for lithium neurotoxicity. Association with lithium doses, duration of treatment, and serum lithium levels will be elucidated. Lastly, diagnosis and treatment considerations will be highlighted. <h3>Conclusions</h3> Chronic lithium Neurotoxicity is more common in the elderly and can occur at normal to even sub therapeutic doses. It is imperative to have an optimal index of suspicion if an individual on chronic lithium therapy presents with cognitive deficits. <h3>Funding</h3> not applicable

Bilateral thalamic infarction secondary to artery of Percheron occlusion: A rare cause of acute coma

An occlusion of the artery of Percheron (AOP) is a rare clinical condition that remains a diagnostic challenge for physicians given its variable presentation. This infarction is a result of an anatomical variant of a single vessel arising from the posterior cerebral artery. Occlusion of the AOP results in variable levels of alteration of consciousness, vertical gaze palsy, and memory impairment. Unfortunately, due to this variable presentation these strokes are often missed. We report a case of a 71 year-old-female who presented with sudden onset of unresponsiveness who was subsequently diagnosed with bilateral thalamic infarction with midbrain involvement secondary to AOP occlusion. Delayed diagnosis can result in poor neurologic outcomes as demonstrated in this case making it imperative to bring further awareness to this clinical syndrome.

Locked-In Syndrome: Practical Rehabilitation Management.

Locked-in syndrome is a rare and devastating condition that results in tetraplegia, lower cranial nerve paralysis, and anarthria with preserved cognition, vertical gaze, and upper eyelid movements. Although acute management is much like that of any severe stroke, rehabilitation and recovery of these patients have not been previously described. Challenges relevant to this population include blood pressure management and orthostasis, timing and appropriateness of reinstating oral feeding, ventilatory support, decannulation after tracheostomy, bowel and bladder management, vestibular dysfunction, and eye care. Targeted rehabilitation of head, neck, and trunk stability to improve function, and proper fit in an appropriate wheelchair are essential to assist with mobility. Rehabilitation interventions should include a focus on distal motor control and upright tolerance training followed by balance and mobility exercises. In addition, special considerations must be given to developing early methods of communication through use of augmentative systems to call for help and express needs. These systems along with additional technology provide the basis to promote connectivity to family and friends through the use of social media and the internet. Establishment of communication, mobility, and connectivity is essential in promoting independence, autonomy, and improving quality of life. Overall, with specialized rehabilitative care and access to the proper equipment, long-term outcomes and quality of life in these patients can be favorable.

Genetic characterization of a cohort with familial parkinsonism and cognitive-behavioral syndrome: A Next Generation Sequencing study

ObjectiveTo perform the genetic characterization of a cohort with familial parkinsonism and cognitive-behavioral syndrome. MethodsA Next Generation Sequencing – based targeted sequencing of 32 genes associated to various neurodegenerative phenotypes, plus a screening for SNCA Copy Number Variations and C9orf72 repeat expansion, was applied in a cohort of 85 Italian patients presenting with parkinsonism and cognitive and/or behavioral syndrome and a positive familial history for any neurodegenerative disorder (i.e., dementia, movement disorders, amyotrophic lateral sclerosis). ResultsThrough this combined genetic approach, we detected potentially relevant genetic variants in 25.8% of patients with familial parkinsonism and cognitive and/or behavioral syndrome. Peculiar phenotypes are described (Cortico-basal syndrome with APP, Posterior Cortical Atrophy with GBA, Progressive Supranuclear Palsy-like with GRN, Multiple System Atrophy with TARDBP).The majority of patients presented a rigid-bradykinetic parkinsonian syndrome, while rest tremor was less common. Myoclonic jerks, pyramidal signs, dystonic postures and vertical gaze disturbances were more frequently associated with the presence of a pathogenic variant in one of the tested genes. ConclusionsGiven the syndromic approach adopted in our study, we were able to provide a detailed clinical description of patients beyond the boundaries of specific clinical diagnoses and describe peculiar phenotypes. This observation further supports the knowledge that genetic disorders present phenotypic overlaps across different neurodegenerative syndromes, highlighting the limitations of current clinical diagnostic criteria defining sharp boundaries between distinct conditions.

Complete Bilateral Horizontal Gaze Palsy as Initial Manifestation of Multiple Sclerosis: A Case Report

Multiple sclerosis is a chronic inflammatory disease of central nervous system that commonly affects young adults. Although ocular movement disturbances are commonly encountered in multiple sclerosis, bilateral horizontal gaze palsy is quite rare. We present a case of young woman presented with dizziness, intractable vomiting and visual disturbances for one week, on examination found to have complete bilateral horizontal gaze palsy while vertical gaze was intact. Brain MRI showed a small lesion in posterior part of medial pontine tegmentum bilaterally which was responsible for patient`s symptoms. She received five doses of one-gram methylprednisolone, her symptoms gradually improved over one week after treatment.