Predicting post-surgical outcomes in idiopathic normal pressure hydrocephalus using clinically important changes from the cerebrospinal fluid tap test.

OBJECTIVE: Patients diagnosed with idiopathic Normal Pressure Hydrocephalus (iNPH) typically experience symptom improvements after undergoing a cerebrospinal fluid-tap test (CSF-TT), These improvements are recognized as indicative of potential improvements following surgical intervention. As gait disturbance is the most common iNPH symptom, gait improvements are of predominant interest. The purpose of this study was to examine if clinically important changes in gait and balance from CSF-TT predict meaningful changes following surgery. METHOD: The study involved analysis of data collected in a prospective observational study for 34 iNPH patients who underwent a CSF-TT and subsequent surgery. Linear regression, logistic regression and classification trees were used for predictive modelling comparing changes from CSF-TT with post-surgical changes in Tinetti, Timed Up and Go (TUG) and Berg Balance Scale (BBS) outcomes. RESULTS: Predictive models for minimal clinically important differences (MCIDs) from CSF-TT to surgery were significant for Tinetti (odds ratio = 1.42, p = 0.02) and BBS (odds ratio = 1.57, p < 0.01). Four items on Tinetti and two items on BBS were identified with a predictive accuracy of 79% and 76% respectively. BBS has the highest sensitivity (85%) and negative predictive value (77%). TUG had a 100% specificity and 100% positive predictive value. The predictive model using MCIDs for TUG was not significant (odds ratio = 1.13, p = 0.06). CONCLUSION: Clinically important changes from CSF-TT are useful in predicting post-surgical outcomes in iNPH patients. Tinetti and BBS, both have predictive value using MCID scores as cut off values, of which BBS is a stronger outcome measure for prediction.

Quantitative gait analysis value as a predictor of shunt surgery effectiveness in normal pressure hydrocephalus: A technical note.

INTRODUCTION: Shunt surgery (SS) remains the most effective treatment for idiopathic Normal pressure hydrocephalus (iNPH), but the selection of the patients with the greatest potential benefit remains elusive. OBJECTIVE: Identify gait features predictive of best response to SS in iNPH. METHODS: Eight patients with iNPH were assessed at baseline, after Cerebrospinal fluid tap-test (CSF-TT) and SS, with clinical scales (Clinical/Patient Global Clinical Impression, EuroQol-5D, Clinical Dementia Rating Scale(CDR), MoCA test, Hoehn-Yahr Scale) and gait analysis with inertial sensors. RESULTS: The 8 included iNPH patients had a mean age of 73 years(59-81), moderate cognitive (CDR-1.5 (0.5-2); MoCA-9.5 (3-21)) and motor impairment (Hoehn-Yahr-2.75(2-3)). After SS, patients had a significant improvement in cognition (MoCA, p = 0.001) and quality of life. At baseline, patients with lower improvement (no change/ minimally improved) (n = 2), in comparison to patient with higher improvement (much/very much improved) (n = 6), already had higher cognitive impairment (MoCa-3(3-3) vs. 11(7-21)). Patients with lower improvement had a lower % of change in gait performance at LP (mean 10.2 %) and were absent of additional benefit after SS(mean -0.8 %). In contrast, gait performance in patients with higher improvement consistently got better from baseline to LP (mean 23.1 %) and from baseline to SS (mean 82.9 %). A significant negative correlation was observed between CDR score and several gait variables: speed (rpb=-0.92,p = 0.009); stride length (rpb=-0.92,p = 0.009); lift-off angle (rpb=-0.96,p = 0.003); and maximum heel (rpb=-0.81,p = 0.049). CONCLUSION: The magnitude of gait improvement after CSF-TT, quantified by gait analysis, can be used as an integral variable in the multimodal clinical approach to the prediction of improvement after SS.

Cerebrospinal fluid biomarkers that reflect clinical symptoms in idiopathic normal pressure hydrocephalus patients.

BACKGROUND: The relationship between cerebrospinal fluid (CSF) biomarkers and the clinical features of idiopathic normal pressure hydrocephalus (iNPH) has been inconclusive. We aimed to evaluate CSF biomarkers reflecting Alzheimer's disease (AD)-related amyloid ß (Aß) aggregation, tau pathology, neuroinflammation and axonal degeneration in relation to the clinical features of pre- and post-shunt surgery in iNPH patients. METHODS: Mini Mental State Examination (MMSE) scores and gait velocity were evaluated pre- and postoperatively in cohorts of 65 Finnish (FIN) and 82 Swedish (SWE) iNPH patients. Lumbar CSF samples were obtained prior to shunt surgery and analysed for soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPß); amyloid-ß isoforms of 42, 40 and 38 (Aß42, Aß40, Aß38); total tau (T-tau); phosphorylated tau (P-tau181); neurofilament light (NfL) and monocyte chemoattractant protein 1 (MCP1). RESULTS: Preoperative patient characteristics showed no significant differences between patients in the FIN and SWE cohorts. Patients in both cohorts had significantly improved gait velocity after shunt surgery (p < 0.0001). Low CSF T-tau and absence of apolipoprotein E ε4 predicted over 20% gait improvement postoperatively (p = 0.043 and p = 0.008). Preoperative CSF T-tau, P-tau181 and NfL correlated negatively with MMSE scores both pre- (p < 0.01) and post-surgery (p < 0.01). Furthermore, T-tau, NfL and Aß42 correlated with MMSE outcomes (p < 0.05). Low preoperative CSF P-tau181 (p = 0.001) and T-tau with NfL (p < 0.001 and p = 0.049) best predicted pre- and postoperative MMSE scores greater than or equal to 26. CONCLUSIONS: CSF biomarkers of neurodegeneration appeared to correlate with pre- and postoperative cognition, providing a window into neuropathological processes. In addition, preoperative CSF neurodegeneration biomarkers may have potential in the prediction of gait and cognitive outcomes after shunt surgery.

The timed up and go test in idiopathic normal pressure hydrocephalus: a Nationwide Study of 1300 patients.

BACKGROUND: The aim of this study was to describe the outcome measure timed up and go (TUG) in a large, nationwide cohort of patients with idiopathic normal pressure hydrocephalus (iNPH) pre- and post-operatively. Furthermore, to compare the TUG test to the 10-m walk test (10MWT), the iNPH scale, the modified Rankin scale (mRS) and the Mini Mental State Examination (MMSE), which are commonly applied in clinical assessment of iNPH. METHODS: Patients with iNPH (n = 1300), registered in the Swedish Hydrocephalus Quality Registry (SHQR), were included. All data were retrieved from the SHQR except the 10MWT, which was collected from patient medical records. Clinical scales were examined pre- and 3 months post-operatively. Data were dichotomised by sex, age, and preoperative TUG time. RESULTS: Preoperative TUG values were 19.0 [14.0-26.0] s (median [IQR]) and 23 [18-30] steps. Post-operatively, significant improvements to 14.0 [11.0-20.0] s and 19 [15-25] steps were seen. TUG time and steps were higher in women compared to men (p < 0.001) but there was no sex difference in improvement rate. Worse preoperative TUG and younger age favoured improvement. TUG was highly correlated to the 10MWT, but correlations of post-operative changes were only low to moderate between all scales (r = 0.22-0.61). CONCLUSIONS: This study establishes the distribution of TUG in iNPH patients and shows that the test captures important clinical features that improve after surgery independent of sex and in all age groups, confirming the clinical value of the TUG test. TUG performance is associated with performance on the 10MWT pre- and post-operatively. However, the weak correlations in post-operative change to the 10MWT and other established outcome measures indicate an additional value of TUG when assessing the effects of shunt surgery.

Acquisition and loss of best walking skills in children and young people with bilateral cerebral palsy.

AIM: To explore factors predicting acquisition and loss of best walking ability in young people with bilateral cerebral palsy (CP). METHOD: In our population cohort (Study of Hips And Physical Experience) of 338 children (201 males, 137 females) with bilateral CP, age at achieving walking was recorded and walking ability predicted from early motor milestones. Walking was assessed at 5 to 8 years (mean 7y) and in 228 of 278 survivors at 13 to 19 years (mean 16y). Parent carers reported their view of any loss of best achieved walking. Factors potentially associated with loss of best achieved walking were explored: severity and type of motor disorder; intellect and communication; manipulative skill; general health and comorbidity; pain; orthopaedic surgery; musculoskeletal spine and lower limb deformity; weight; fatigue; mood; and presence of regular exercise regime. RESULTS: The ability to walk independently was reliably predicted by the motor milestone 'getting to sit and maintain sitting' by the age of 36 months (without aids) and 55 months (with aids). Forty-five per cent of the cohort never walked 10 steps independently. Not all who achieved walking without aids were still doing so by a mean age of 16 years, which was associated with later age at achieving walking and the degree of musculoskeletal deformity, as was the parent carers' report of loss of best walking. INTERPRETATION: In this study, development of musculoskeletal deformity was a significant factor in not maintaining best achieved walking by mean age 16 years, which is most likely to occur in young people whose walking ability is with aids over short distances or in therapy only. Prediction of future walking ability in a child with bilateral CP can be made from early motor milestones.

A-GAS: A Probabilistic Approach for Generating Automated Gait Assessment Score for Cerebral Palsy Children.

Gait disorders in children with cerebral palsy (CP) affect their mental, physical, economic, and social lives. Gait assessment is one of the essential steps of gait management. It has been widely used for clinical decision making and evaluation of different treatment outcomes. However, most of the present methods of gait assessment are subjective, less sensitive to small pathological changes, time-taking and need a great effort of an expert. This work proposes an automated, comprehensive gait assessment score (A-GAS) for gait disorders in CP. Kinematic data of 356 CP and 41 typically developing subjects is used to validate the performance of A-GAS. For the computation of A-GAS, instance abnormality index (AII) and abnormality index (AI) are calculated. AII quantifies gait abnormality of a gait cycle instance, while AI quantifies gait abnormality of a joint angle profile during walking. AII is calculated for all gait cycle instances by performing probabilistic and statistical analyses. Abnormality index (AI) is a weighted sum of AII, computed for each joint angle profile. A-GAS is a weighted sum of AI, calculated for a lower limb. Moreover, a graphical representation of the gait assessment report, including AII, AI, and A-GAS is generated for providing a better depiction of the assessment score. Furthermore, the work compares A-GAS with a present rating-based gait assessment scores to understand fundamental differences. Finally, A-GAS's performance is verified for a high-cost multi-camera set-up using nine joint angle profiles and a low-cost single camera set-up using three joint angle profiles. Results show no significant differences in performance of A-GAS for both the set-ups. Therefore, A-GAS for both the set-ups can be used interchangeably.

The case of a 30-year-old man with subacute gait instability, weakness, and muscle spasms.

A 30-year-old healthy man presents after a fall with diffuse weakness and pain and recent onset left eye ptosis in the setting of three weeks of progressive bilateral leg weakness, gait instability, and difficulty washing his hair due to upper extremity weakness. He had also developed stiffness in his neck and shoulders and uncontrollable muscle spasms. Exam was notable for ptosis, fatiguing weakness in extremities, increased tone, hyperreflexia with clonus, and spastic gait. A mediastinal mass was found on chest CT (Fig. 1), and biopsy confirmed an invasive thymoma with positive nodes. Serum testing was positive for antibodies to acetylcholine receptors as well as glutamic acid decarboxylase.

Missed Opportunities to Diagnose and Intervene in Modifiable Risk Factors for Older Emergency Department Patients Presenting After a Fall.

STUDY OBJECTIVE: Falls are a major cause of mortality and morbidity in adults aged 65 years and older and a common chief complaint in the emergency department (ED). However, the rate of missed opportunities to diagnose and intervene in modifiable fall-risk factors in the ED is unknown. We hypothesize that although ED providers (defined as ED attendings, residents, and advanced care providers) excel at assessing and ruling out injury, they miss the opportunity to identify a large portion of the modifiable risk factors that contribute to a patient's fall. Our objective is to quantify the number of missed opportunities to identify and reduce fall-risk factors in older adult ED patients presenting after a fall. METHODS: This secondary analysis used data from a prospective cohort study of older patients at a single academic urban ED. The original study investigated the standard ED evaluation after a fall in older adults. All patients in the original study had a falls evaluation conducted at their ED visit by trained research assistants; this served as the standard fall evaluation. We reviewed the charts of study patients and identified modifiable fall-risk factors. We then determined the number of missed opportunities to intervene in these risk factors during the ED encounter; the primary outcome was the percentage of missed opportunities to identify risk factors in older ED patients who fell. RESULTS: We found that of the 400 patient charts reviewed, 349 patients had a modifiable risk factor for falling. Of those patients with known modifiable risk factors, the ED team missed identifying the factors in 335 patients (96%). The most commonly missed fall-risk factors were visual acuity (147/154; 96%) and the use of high-risk medications (245/259;95%). Gait abnormalities had the lowest rates of missed modifiable risk factors, at 56% of patients (109/196). When a modifiable risk factor was identified and intervened in, it was most commonly done in the ED observation unit by a physician or physical therapist, and often consisted of an outpatient referral or primary care physician follow-up. CONCLUSION: Providers frequently fail to identify and intervene in modifiable fall-risk factors in older adult patients presenting to the ED after a fall; this is a missed opportunity. Addressing the risk factors that contributed to the fall during a fall-related ED visit may minimize fall risk and promote safer mobility.

Degos disease: A radiological-pathological correlation of the neuroradiological aspects of the disease.

Malignant atrophic papulosis (Degos disease) is an unusual thrombotic microangiopathy of uncertain etiology. The disease characteristically involves the skin and internal organs, with nervous system involvement more common in children. We present a case with diverse neurological manifestations including cranial nerve palsies, gait instability, and urinary incontinence. The patient also developed white papular lesions on her lower extremities and back. Magnetic resonance imaging (MRI) demonstrated progressive intracranial and spinal abnormalities. Despite treatment with numerous biologic agents, the patient had persistent clinical deterioration and expired one month after admission. We highlight the extensive neurologic manifestations of Degos disease correlated with neuroradiological imaging and pathological features. Nervous system involvement in Degos disease requires careful neurologic and dermatologic exam with central nervous system (CNS) magnetic resonance imaging to distinguish it from non-organic etiologies of similar symptoms.

Prevalence of Alternative Diagnoses and Implications for Management in Idiopathic Normal Pressure Hydrocephalus Patients.

BACKGROUND: Following Bayes theorem, ventriculomegaly and ataxia confer only a 30% chance of idiopathic Normal Pressure Hydrocephalus (NPH). When coupled with positive responses to best diagnostic testing (extended lumbar drainage), 70% of patients recommended for shunting will not actually have NPH. This is inadequate clinical care. OBJECTIVE: To determine the proportion of alternative and treatable diagnoses in patients referred to a multidisciplinary NPH clinic. METHODS: Patients without previously diagnosed NPH were queried from prospectively collected data. At least 1 neurosurgeon, cognitive neurologist, and neuropsychologist jointly formulated best treatment plans. RESULTS: Of 328 total patients, 45% had an alternative diagnosis; 11% of all patients improved with treatment of an alternative diagnosis. Of 87 patients with treatable conditions, the highest frequency of pathologies included sleep disorders, and cervical stenosis, followed by Parkinson disease. Anti-cholinergic burden was a contributor for multiple patients. Of 142 patients undergoing lumbar puncture, 71% had positive responses and referred to surgery. Compared to NPH patients, mimickers were statistically significantly older with lower Montreal Cognitive Assessment (MoCA) score and worse gait parameters. Overall, 26% of the original patients underwent shunting. Pre-post testing revealed a statistically significant improved MoCA score and gait parameters in those patients who underwent surgery with follow-up. CONCLUSION: Because the Multidisciplinary NPH Clinic selected only 26% for surgery (corroborating 30% in Bayes theorem), an overwhelming majority of patients with suspected NPH will harbor alternative diagnoses. Identification of contributing/confounding conditions will support the meticulous work-up necessary to appropriately manage patients without NPH while optimizing clinical responses to shunting in correctly diagnosed patients.

Superficial siderosis and intracranial hypotension syndrome following brachial plexus avulsion injury. A case of surgical treatment.

Superficial siderosis (SS) is a slowly progressive neurodegenerative disorder caused by persistent or intermittent bleeding into the subarachnoid space. It leads to characteristic clinical and radiographic findings. Dural pathology is believed to be the most common identifiable etiology of SS. It has been suggested that dural tear may be the common pathology of both SS and intracranial hypotension syndrome. We present a patient with SS caused by posttraumatic duropathy that was associated with cerebrospinal fluid (CSF) hypotension headache. Patient was treated surgically with stabilization of neurological deficit and orthostatic headache improvement. It supports the speculated link between both entities and may confirm surgery being a reasonable approach in patients with SS.

The effect of mono- versus multi-segment musculoskeletal models of the foot on simulated triceps surae lengths in pathological and healthy gait.

BACKGROUND: Estimating muscle-tendon complex (MTC) lengths is important for planning of soft tissue surgery and evaluating outcomes, e.g. in children with cerebral palsy (CP). Conventional musculoskeletal models often represent the foot as one rigid segment, called a mono-segment foot model (mono-SFM). However, a multi-segment foot model (multi-SFM) might provide better estimates of triceps surae MTC lengths, especially in patients with foot deformities. RESEARCH QUESTION: What is the effect of a mono- versus a multi-SFM on simulated ankle angles and triceps surae MTC lengths during gait in typically developing subjects and in children with CP with equinus, cavovarus or planovalgus foot deformities? METHODS: 50 subjects were included, 10 non-affected adults, 10 typically developing children, and 30 children with spastic CP and foot deformities. During walking trials, marker trajectories were collected for two marker models, including a mono- and multi-segment foot; respectively Newington gait model and Oxford foot model. Two musculoskeletal lower body models were constructed in OpenSim with either a mono- or multi-SFM based on the corresponding marker models. Normalized triceps surae MTC lengths (soleus, gastrocnemius medialis and lateralis) and ankle angles were calculated and compared between models using statistical parametric mapping RM-ANOVAs. Root mean square error values between simulated MTC lengths were compared using Wilcoxon signed-rank and rank-sum tests. RESULTS: Mono-SFM simulated significantly more ankle dorsiflexion (7.5 ± 1.2°) and longer triceps surae lengths (difference; soleus:2.6 ± 0.29 %, gastrocnemius medialis:1.7 ± 0.2 %, gastrocnemius lateralis:1.8 ± 0.2%) than a multi-SFM. Differences between models were larger in children with CP compared to typically developing children and larger in the stance compared to the swing phase of gait. Largest differences were found in children with CP presenting with planovalgus (4.8 %) or cavovarus (3.8 %) foot deformities. SIGNIFICANCE: It is advisable to use a multi-SFM in musculoskeletal models when simulating triceps surae MTC lengths, especially in individuals with planovalgus or cavovarus foot deformities.

Vemurafenib as first-line therapy in BRAF-V600E-mutant Erdheim-Chester disease with CNS involvement.

Erdheim-Chester disease (ECD) is a rare histiocytosis that may affect the central nervous system (CNS). Infiltration by the disease occurs throughout the neuroaxis, usually involving the dentate nucleus and the pons, manifested as a pyramido-cerebellar syndrome. CNS involvement is an adverse prognostic factor which warrants prompt evaluation and treatment. BRAF mutation occurs in more than half of the cases and has become central in the therapeutic approach. There is rapidly growing evidence that BRAF inhibitors such as vemurafenib or dabrafenib are effective in treating CNS-spread disease. We present a patient with BRAF-V600E-mutant ECD with a classical pyramido-ataxic onset of disease who improved after prompt diagnosis with vemurafenib treatment as first-line therapy.

Unusual case of Juvenile Tay-Sachs disease.

Tay-Sachs disease (TSD) is a type 1 gangliosidosis (GM2) and caused by hexosaminidase A deficiency resulting in abnormal sphingolipid metabolism and deposition of precursors in different organs. It is a progressive neurodegenerative disorder transmitted in an autosomal-recessive manner. There is an accumulation of GM2 in neurocytes and retinal ganglions which result in progressive loss of neurological function and formation of the cherry-red spot which is the hallmark of TSD. We report the first case of juvenile TSD from Pakistan in a child with death of an older sibling without the diagnosis.

Acute Presentation of Lumbar Spinal Stenosis Due to Ossified Ligamentum Flavum: The Possible Role of Spondylolisthesis: A Case Report.

CASE: A 64-year-old woman with a history of low back pain, presented with acute gait impairment and lower limbs numbness without any history of trauma. Imaging studies revealed ossification of the ligamentum flavum (OLF) at L4-L5 and concomitant spondylolisthesis. Decompression surgery with en-bloc removal including the laminae, the ossified ligamentum flavum, and the medial facet and posterior stabilization was performed resulting in complete immediate recovery. CONCLUSIONS: This report is the first to describe a case of an acute nontraumatic presentation of OLF associated with spondylolisthesis. OLF pathogenesis in still unknown, although several factors have been considered. According to the literature, operative treatment has demonstrated to be effective.

Congelamento da marcha e de membros superiores na doença de Parkinson / Freezing of gait and upper limbs in Parkinson's disease

O fenômeno do congelamento é considerado um sintoma incapacitante para indivíduos acometidos pela doença de Parkinson, gerando impactos negativos na mobilidade, funcionalidade e qualidade de vida. O congelamento pode acometer membros inferiores (congelamento da marcha) e/ou membros superiores, sendo caracterizado por súbita incapacidade de iniciar ou manter a amplitude dos movimentos. A fisiopatologia do congelamento ainda não é compreendida, porém atribui-se às alterações em diferentes estruturas neuroanatômicas, tais como: núcleo pedúnculo-pontino, locus ceruleus, circuitaria dos núcleos da base, pedúnculo cerebelar e córtices cerebrais e sistema límbico. Fatores que contribuem para o surgimento do congelamento são: tempo de duração da doença, idade avançada, subtipo acinético-rígido da doença, ansiedade ou depressão, perfil de tratamento farmacológico. Sugere-se que o congelamento da marcha e dos membros superiores compartilhem das mesmas características espaço-temporais. A avaliação clínica do congelamento da marcha é melhor estabelecida quando comparada com a avaliação do congelamento dos membros superiores. Estratégias para minimizar o fenômeno do congelamento são descritas no presente artigo.

The phenomenon of freezing is a disabling symptom for subjects with Parkinson's disease, causing impairment in mobility, functionality and quality of life. Freezing may affect lower limbs (freezing of gait) or upper limbs, and is characterized by sudden inability to initiate or maintain range of motion. The pathophysiology of freezing is not yet understood, but it is attributed to changes in different neuroanatomical structures, such as: pedunculopontine nucleus, locus ceruleus, basal ganglia circuitry, pedunculocerebellar and cerebral cortices and limbic system. Factors that contribute to the appearance of freezing are: advanced age, akinetic-rigid subtype of the disease, anxiety or depression, pharmacological treatment strategies. It is suggested that the freezing of gait and upper limbs share the same spatiotemporal characteristics. The clinical evaluation of freezing of gait is better established when compared to the freezing of upper limbs. Strategies to minimize the phenomenon of freezing are described in this article.