Upper limb dysfunction and activities in daily living in idiopathic normal pressure hydrocephalus

Background Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease with a characteristic symptom triad of gait disturbance, cognitive decline, and incontinence. Recently, also dysfunctions in upper limbs have been described in iNPH and reported to improve after shunt surgery. We aim to describe the role of upper limb motor function in the clinical assessment of iNPH patients and its influence on activities of daily living (ADL). Methods Seventy-five consecutive patients with probable iNPH were studied pre-operatively and at 3 and 12 months after shunt surgery. The pre-operative evaluation included lumbar drainage of cerebrospinal fluid (tap test). Motor functions were assessed in upper and lower limbs with Grooved Pegboard Test (GPT), Box & Block Test (BBT), Total Score of Gait (TSG), and balance test. ADL was assessed with Barthel's index and cognition in accordance with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Results Patients showed improvement in all motor tests and ADL at 3 months after shunt surgery. The improvement remained stable during the 12-month post-operative follow-up. The motor function tests correlated with each other and with ADL. Conclusions A 3-month follow-up period after shunt surgery is adequate to show improvement in motor tasks, and a positive outcome will last for at least 12 months. A shunt-responsive dysfunction of upper limb motor performance plays a major role in ADL of iNPH patients. Therefore, we suggest an evaluation of upper limb motor performance to be included in routine evaluation of iNPH patients.Peer reviewe

Genome-wide assessment of the association of rare and common copy number variations to testicular germ cell cancer.

Testicular germ cell cancer (TGCC) is one of the most heritable forms of cancer. Previous genome-wide association studies have focused on single nucleotide polymorphisms (SNPs), largely ignoring the influence of copy number variants (CNVs). Here we present a genome-wide study of copy number variation on a cohort of 212 cases and 437 controls from Denmark, which was genotyped at ~1.8 million markers, half of which were non-polymorphic copy number markers. No association of common variants were found, whereas analysis of rare variants (present in less than 1% of the samples) initially indicated a single gene with significantly higher accumulation of rare CNVs in cases as compared to controls, at the gene PTPN1 (P=3.8*10-2, 0.9% of cases and 0% of controls). However, the CNV could not be verified by qPCR in the affected samples. The CNV calling of the array data was validated by sequencing of the GSTM1 gene, which showed that the CNV frequency was in complete agreement between the two platforms. This study therefore disconfirms the hypothesis that there exists a single CNV locus with a major effect size that predisposes to TGCC. Genome-wide pathway association analysis indicated a weak association of rare CNVs related to cell migration (FDR=0.021, 1.8% of cases and 1.1% of controls). Dysregulation during migration of primordial germ cells has previously been suspected to be a part of TGCC development and this set of multiple rare variants may thereby have a minor contribution to an increased susceptibility of TGCCs

In vivo assessment of Lewy body and beta-amyloid copathologies in idiopathic normal pressure hydrocephalus: prevalence and associations with clinical features and surgery outcome

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a clinico-radiological syndrome of elderly individuals likely sustained by different neurodegenerative changes as copathologies. Since iNPH is a potentially reversible condition, assessing neurodegenerative pathologies in vitam through CSF biomarkers and their influence on clinical features and surgical outcome represents crucial steps.Methods: We measured a-synuclein seeding activity related to Lewy body (LB) pathology by the real-time quaking-induced conversion assay (RT-QuIC) and Alzheimer disease core biomarkers (proteins total-tau, phospho-tau, and amyloid-beta) by immunoassays in the cerebrospinal fluid (CSF) of 293 iNPH patients from two independent cohorts. To compare the prevalence of LB copathology between iNPH participants and a control group representative of the general population, we searched for a-synuclein seeding activity in 89 age-matched individuals who died of Creutzfeldt-Jakob disease (CJD). Finally, in one of the iNPH cohorts, we also measured the CSF levels of neurofilament light chain protein (NfL) and evaluated the association between all CSF biomarkers, baseline clinical features, and surgery outcome at 6 months.Results: Sixty (20.5%) iNPH patients showed alpha-synuclein seeding activity with no significant difference between cohorts. In contrast, the prevalence observed in CJD was only 6.7% (p= 0.002). Overall, 24.0% of iNPH participants showed an amyloid-positive (A+) status, indicating a brain co-pathology related to A beta deposition. At baseline, in the Italian cohort, a-synuclein RT-QuIC positivity was associated with higher scores on axial and upper limb rigidity (p=0.003 and p =0.011, respectively) and lower MMSEc scores (p =0.003). A+ patients showed lower scores on the MMSEc (p =0.037) than A- patients. Higher NfL levels were also associated with lower scores on the MMSEc (rho = -0.213; p= 0.021). There were no significant associations between CSF biomarkers and surgical outcome at 6 months (i.e. responders defined by decrease of 1 point on the mRankin scale).Conclusions: Prevalent LB- and AD-related neurodegenerative pathologies affect a significant proportion of iNPH patients and contribute to cognitive decline (both) and motor impairment (only LB pathology) but do not significantly influence the surgical outcome at 6 months. Their effect on the clinical benefit after surgery over a more extended period remains to be determined

Outcome and complications of operatively treated subaxial cervical spine injuries: A population-based retrospective cohort study

Objective: The aim was to study the outcome and complications of operative treatment for subaxial cervical spine injuries with respect to injury morphology and surgical strategy. Methods: A population-based cohort of 271 consecutive patients treated at Kuopio University Hospital from 2003 to 2018 was retrospectively reviewed. Results: The mean age was 52.4 (range 12–90) years and 78.6% were male. The AOSpine morphological classification was C in 56.5%, B in 24.7% and A in 17.0% of cases. The surgical approach was anterior in 70.8%, posterior in 20.3% and combined in 8.9% of patients. Fixation alignment was maintained in 96.9% of patients. Instrumentation failures were observed only in patients operated anteriorly but no statistical difference was found between the surgical approaches. The American Spinal Injury Association Impairment Scale (AIS) grade improved in 22.1% of patients. Patients with preoperative AIS grade C had significant potential for neurological improvement (OR 10.44; 95% CI 1.77–61.56; p = 0.010). Postoperative, mostly mild, complications manifested in 22.5% of patients. The posterior approach was associated with fewer postoperative complications (OR 0.18; 95% CI 0.06–0.51; p = 0.001). Preoperative AIS grade A was a significant predisposing factor for complications (OR = 4.90; 95% CI = 1.49–16.10; p = 0.009). The perioperative (90-day) mortality rate was 3.3%. The mean follow-up period was 64.7 ± 25.9 (radiological)/136.7 ± 174.8 (clinical) days. Conclusions: Operative treatment is safe and effective but the surgical approach should be patient- and injury-specific. The prognosis for neurological recovery from spinal cord injury is superior in patients with partially preserved motor function

Additional file 3 of The effect of shunt surgery on corticospinal excitability in idiopathic normal pressure hydrocephalus: a transcranial magnetic stimulation study

Additional file 3. Data of good responders and limited responders at baseline, TAP and follow-up

Additional file 2 of The effect of shunt surgery on corticospinal excitability in idiopathic normal pressure hydrocephalus: a transcranial magnetic stimulation study

Additional file 2. Individual follow-up data of shunted and not shunted patients

Additional file 1 of The effect of shunt surgery on corticospinal excitability in idiopathic normal pressure hydrocephalus: a transcranial magnetic stimulation study

Additional file 1. Data of shunted and not shunted patients at baseline, at TAP and at follow-up

Corticospinal excitability in idiopathic normal pressure hydrocephalus:a transcranial magnetic stimulation study

Abstract Background: Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease with an unknown etiology. Disturbed corticospinal inhibition of the motor cortex has been reported in iNPH and can be evaluated in a noninvasive and painless manner using navigated transcranial magnetic stimulation (nTMS). This is the first study to characterize the immediate impact of cerebrospinal fluid (CSF) drainage on corticospinal excitability. Methods: Twenty patients with possible or probable iNPH (16 women and 4 men, mean age 74.4 years, range 67–84 years), presenting the classical symptom triad and radiological findings, were evaluated with motor function tests (10-m walk test, Grooved Pegboard and Box & Block test) and nTMS (silent period, SP, resting motor threshold, RMT and input–output curve, IO-curve). Evaluations were performed at baseline and repeated immediately after CSF drainage via lumbar puncture. Results: At baseline, iNPH patients presented shorter SPs (p < 0.001) and lower RMTs (p < 0.001) as compared to normative values. Positive correlation was detected between SP duration and Box & Block test (rho = 0.64, p = 0.002) in iNPH patients. CSF drainage led to an enhancement in gait velocity (p = 0.002) and a steeper IO-curve slope (p = 0.049). Conclusions: Shorter SPs and lower RMTs in iNPH suggest impaired corticospinal inhibition and corticospinal hyperexcitability. The steeper IO-slope in patients who improve their gait velocity after CSF drainage may indicate a higher recovery potential. Corticospinal excitability correlated with the motor function of the upper limbs implying that the disturbance in motor performance in iNPH extends beyond the classically reported gait impairment