Nerve ultrasound as a diagnostic tool for sensory neuronopathy in spinocerebellar ataxia syndrome

ObjectiveThe objective was to assess if nerve ultrasound has a role in diagnosing sensory neuronopathy in spinocerebellar ataxia syndrome (SCA) by examining if proposed diagnostic cut-off criteria of ultrasound in sensory neuronopathy caused by cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS) were also discriminatory for SCA-related sensory neuronopathy.MethodsOptimal diagnostic cut-off criteria for nerve size measured by diagnostic ultrasound were developed in 14 patients with CANVAS and 42 healthy controls using six peripheral nerve sites; and logistic regression and receiver operating characteristic (ROC) curves. These proposed cut-off values were tested in seven patients with spinocerebellar ataxia type 2 (SCA2) patients with sensory neuronopathy.ResultsUltrasound of upper limb nerves was highly accurate in differentiating between CANVAS and healthy controls with areas under the ROC curves between 0.97 and 0.99. Optimal cut-off measurements from the CANVAS patients also accurately diagnosed sensory neuronopathy in all patients with SCA2.ConclusionsUpper limb ultrasound is a sensitive tool for detecting sensory neuronopathy in established cases of CANVAS and SCA2.SignificanceUltrasound could aid the diagnosis of sensory neuronopathy in spinocerebellar ataxias.     

Myelin protein zero gene dose dependent axonal ion-channel dysfunction in a family with Charcot-Marie-Tooth disease

ObjectiveThe myelin impairment in demyelinating Charcot-Marie-Tooth (CMT) disease leads to various degrees of axonal degeneration, the ultimate cause of disability. We aimed to assess the pathophysiological changes in axonal function related to the neuropathy severity in hypo-/demyelinating CMT patients associated with myelin protein zero gene (MPZ) deficiency.MethodsWe investigated four family members (two parents and two sons) harboring a frameshift mutation (c.306delA, p.Asp104ThrfsTer14) in the MPZ gene, predicted to result in a nonfunctional P₀, by conventional conduction studies and multiple measures of motor axon excitability. In addition to the conventional excitability studies of the median nerve at the wrist, we tested the spinal accessory nerves. Control measures were obtained from 14 healthy volunteers.ResultsThe heterozygous parents (aged 56 and 63) had a mild CMT1B whereas their two homozygous sons (aged 31 and 39 years) had a severe Dejerine-Sottas disease phenotype. The spinal accessory nerve excitability could be measured in all patients. The sons showed reduced deviations during depolarizing threshold electrotonus and other depolarizing features which were not apparent in the accessory and median nerve studies of the parents. Mathematical modeling indicated impairment in voltage-gated sodium channels. This interpretation was supported by comparative modeling of excitability measurements in MPZ deficient mice.ConclusionOur data suggest that axonal depolarization in the context of abnormal voltage-gated sodium channels precedes axonal degeneration in severely hypo-/demyelinating CMT as previously reported in the mouse models.SignificanceMeasures of the accessory nerve excitability could provide pathophysiological markers of neurotoxicity in severe demyelinating neuropathies.     

Visualization of electrical activity in the cervical spinal cord and nerve roots after ulnar nerve stimulation using magnetospinography

ObjectiveTo establish a method for magnetospinography (MSG) measurement after ulnar nerve stimulation and to clarify its characteristics.MethodsUsing a 132-channel magnetoneurography system with a superconducting quantum interference device, cervical MSG measurements were obtained for 10 healthy volunteers after stimulation of the ulnar nerve at the elbow and the wrist, and neural current distribution was calculated and superimposed on the cervical X-ray images.ResultsNeuromagnetic signals were obtained in all participants after applying the stimulus artifact removal algorithm. The measured magnetic field intensity after elbow stimulation was about twice that after wrist stimulation. Calculated neural currents flowed into the intervertebral foramina at C6/7 to T1/2 and propagated cranially along the spinal canal. The conduction velocity from the peak latency of inward currents at C5-C7 was 73.4 ± 19.6 m/s.ConclusionsWe successfully obtained MSG measurements after ulnar nerve stimulation. The neural currents flowed into the spinal canal from more caudal segments after ulnar nerve stimulation compared with median nerve stimulation, and these MSG measurements were effective in examining the spinal tracts at C5/6/7.SignificanceThis is the first report on the use of MSG to visualize electrical activity in the cervical spinal cord and nerve root after ulnar nerve stimulation.     

Age-related characteristics and normative values of F waves in healthy infants

ObjectiveTo establish age-related characteristics and normative values of F waves in healthy Chinese infants.MethodsWe studied median, ulnar and tibial nerves on one side distally in 229 healthy Chinese infants (108 males) ranging from 1 to 12 months old.ResultsMinimal F-wave latencies (Fmin) showed a strong negative correlation to the age for median, ulnar and tibial nerves (P < 0.01) but no correlation to the height. Statistical analyses revealed a significant (P < 0.01) decrease of Fmin during the second month of life and no change (P > 0.05) thereafter. Dividing the infants into 1 month old (Group 1) and 2–12 months old (Group 2), normal values (Mean ± SD ms) of Fmin for tibial, median and ulnar nerves consisted of 23.38 ± 1.68, 17.19 ± 0.95 and 16.47 ± 1.06 for Group 1 and 21.42 ± 1.25, 14.50 ± 1.15 and 14.52 ± 0.90 for Group 2.ConclusionF-wave latencies shorten in the 2nd month of life and change little thereafter when age-related maturation counters the concomitant growth of the nerve length.SignificanceF waves can assess infantile neuropathies as a reliable measure, complementing the technically difficult conventional nerve conduction study in short limbs.     

Novel functional imaging technique for the brachial plexus based on magnetoneurography

ObjectiveTo visualize neural activity in the brachial plexus using magnetoneurography (MNG).MethodsUsing a 124- or 132-channel biomagnetometer system with a superconducting quantum interference device, neuromagnetic fields above the clavicle and neck region were recorded in response to electrical stimulation of the median and ulnar nerves in five asymptomatic volunteers (four men and one woman; age, 27–45 years old). Equivalent currents were computationally reconstructed from neuromagnetic fields and visualized as pseudocolor maps. Reconstructed currents at the depolarization site and compound nerve action potentials (CNAPs) at Erb’s point were compared.ResultsNeuromagnetic fields were recorded in all subjects. The reconstructed equivalent currents propagated into the vertebral foramina, and the main inflow levels differed between the median nerve (C5/C6–C7/T1 vertebral foramen) and the ulnar nerve (C7/T1–T1/T2). The inward current peaks at the depolarization site and CNAPs showed high linear correlation.ConclusionsMNG visualizes neural activity in the brachial plexus and can differentiate the conduction pathways after median and ulnar nerve stimulations. In addition, it can visualize not only the leading and trailing components of intra-axonal currents, but also inward currents at the depolarization site.SignificanceMNG is a novel and promising functional imaging modality for the brachial plexus.     

Neuropathy in sporadic inclusion body myositis: A multi-modality neurophysiological study

ObjectiveSporadic inclusion body myositis (sIBM) has been associated with neuropathy. This study employs nerve excitability studies to re-examine this association and attempt to understand underlying pathophysiological mechanisms.MethodsTwenty patients with sIBM underwent median nerve motor and sensory excitability studies, clinical assessments, conventional nerve conduction testing (NCS) and quantitative thermal threshold studies. These results were compared to established normal controls, or results from a normal cohort of older control individuals.ResultsSeven sIBM patients (35%) demonstrated abnormalities in conventional NCS, with ten patients (50%) demonstrating abnormalities in thermal thresholds. Median nerve motor and sensory excitability differed significantly in sIBM patients when compared to normal controls. None of these neurophysiological markers correlated significantly with clinical markers of sIBM severity.ConclusionA concurrent neuropathy exists in a significant proportion of sIBM patients, with nerve excitability studies revealing changes possibly consistent with axolemmal depolarization or concurrent neuronal adaptation to myopathy. Neuropathy in sIBM does not correlate with muscle disease severity and may reflect a differing tissue response to a common pathogenic factor.SignificanceThis study affirms the presence of a concurrent neuropathy in a large proportion of sIBM patients that appears independent of the severity of myopathy.     

Expanding the clinical and EEG spectrum of CNKSR2-related encephalopathy with status epilepticus during slow sleep (ESES)

ObjectiveTo investigate the clinical and EEG features of Encephalopathy with Status Epilepticus during slow Sleep (ESES) related to CNKSR2 pathogenic variants.MethodsDetailed clinical history, repeated wakefulness/overnight sleep EEGs, brain MRI were collected in five patients, including one female, with CNKSR2-related ESES.ResultsNeurodevelopment in infancy was normal in two patients, delayed in three. Epilepsy onset (age range: 2–6 years) was associated with appearance or aggravation of cognitive impairment, language regression and/or behavioral disorders. Worsening of epilepsy and of cognitive/behavioral disturbances paralleled by enhancement of non-rapid eye movement (NREM) sleep-related, frontally predominant, EEG epileptic discharges [spike-wave-index (SWI): range 60–96%] was consistent with ESES. In three patients, episodes of absence status epilepticus or aggravation of atypical absences occurred, in this latter case associated with striking increment of awake SWI. Speech/oro-motor dyspraxia was diagnosed in four patients. In two patients, long-term follow-up showed epilepsy remission and persistence of mild/moderate cognitive disorders and behavioral disturbances into adulthood.ConclusionsNovel findings of our study are occurrence also in females, normal neurodevelopment before epilepsy onset, epilepsy aggravation associated with enhanced awake SWI, mild/moderate evolution in adulthood and language disorder due to speech/oro-motor dyspraxia.SignificanceOur findings expand the phenotypic spectrum of CNKSR2-related ESES.     

Deriving pediatric nerve conduction normal values in the very young (<3 years)

ObjectiveThis work describes our efforts to obtain nerve conduction studies normal values in a pediatric cohort between birth and 3 years of age using the extrapolated norms or e-norms method. Interpretation of these studies poses major challenges when no reliable normal values can be found in the literature.MethodsThe e-norms method was used to derive a reference range of upper and lower extremity sensory and motor nerve conductions normal values from a pediatric cohort referred to an EMG Laboratory for nerve conduction studies.ResultsE-norms were calculated for Median, Ulnar, Superficial Peroneal, Sural, and Medial Plantar sensory studies, and for Median, Ulnar, Peroneal, and Tibial motor studies.ConclusionsPediatric electrodiagnostic testing is a very challenging undertaking. The ability to obtain and use normal values from the neurophysiologist’s own referral pool adds great value to their diagnostic work-up.SignificanceEMG and nerve conduction studies can yield invaluable information in the diagnostic work-up of young infants. Using the e-norms method improves on the analysis and interpretation of electrophysiological studies in this age group.     

Cerebral fat embolism syndrome at a single trauma center

ObjectivesBased on a 16-year case series, we sought lessons about diagnosis and treatment of cerebral fat embolism syndrome.Materials and methodsUsing discharge codes at a Level 1 Trauma Center, we performed a retrospective chart review of clinical characteristics, diagnostic studies, treatments, and outcome in cerebral fat embolism syndrome.ResultsThirty-nine (40%) of 97 patients with fat embolism syndrome were diagnosed with cerebral fat embolism syndrome, with 29 (74%) presenting with coma. All had abnormal brain magnetic resonance imaging, with scattered cytotoxic edema (starfield pattern) in 29 (74%). All but two of the 21 patients with dilated fundoscopy showed retinal embolism. Among 29 patients with transcranial Doppler, the presence of microembolic signals in 15 (52%) was associated with fever (p = 0.039), right-to-left intracardiac shunting (p = 0.046) and a trend towards initial coma. In 11 patients with serial transcranial Dopplers and treatment with high-intensity statin therapy, the frequency of microembolic signals tended to decrease after therapy was initiated. Of the 28 (72%) of the 39 patients discharged, 16 (57%) had mild to moderate disability at last follow up.ConclusionsThe recognition of cerebral fat embolism syndrome may be improved with routine inclusion of brain magnetic resonance imaging, dilated fundoscopy, and transcranial Doppler. We share our empiric management algorithm for cerebral fat embolism syndrome using these studies and with consideration of experimental therapies in select patients to prevent ongoing cerebral injury.     

Myoclonic super-refractory status epilepticus with favourable evolution in a teenager with FIRES: Is the association of vagus nerve stimulation and cannabidiol effective?

BackgroundFebrile infection-related epilepsy syndrome (FIRES) is a rare and catastrophic clinical syndrome occurring in previously healthy patients. Aetiology is still unknown and outcome usually poor. We describe a case of myoclonic prolonged super refractory status epilepticus (P-SRSE) in FIRES in a patient admitted to the paediatric intensive care unit of Padova, Italy.Case reportA previously healthy 14-year-old girl with onset of myoclonic status epilepticus after a mild febrile illness was admitted to our hospital with a diagnosis of FIRES. Extensive diagnostic work-up was inconclusive. Status epilepticus and electroclinical seizures recurred every time weaning from anaesthetic agents was attempted. Eventually, a vagal nerve stimulator (VNS) was implanted and cannabidiol (CBD) administered, 43 days and 70 days after P-SRSE onset, respectively. Two days after CBD introduction, status epilepticus weaned and the girl rapidly regained complete consciousness showing a brilliant and unexpected recovery. At last follow-up, 12 months later, she is 8-months seizure free on multiple antiseizure medications, has only mild neuropsychological impairment with no neurological and intellective deficit.ConclusionsTo our knowledge, this represents a unique case with an extremely favourable evolution with a possible effect of the association of VNS and CBD to traditional antiseizure medications.     

Median somatosensory evoked potential as a predictor of clinical outcome after urgent surgical extracranial internal carotid artery recanalization

ObjectiveChanges in the N20/P25 amplitude of somatosensory evoked potentials (SEP) of the median nerve have been found to correlate with those in cortical regional cerebral blood flow (rCBF). Our study presents the use of median nerve SEP amplitude in predicting the clinical outcome of urgent surgical internal carotid artery (ICA) recanalization.MethodsA total of 27 patients suffering an acute ischemic stroke (AIS) with extracranial ICA occlusion within 24 h were prospectively recruited. The primary preoperative endpoints included the SEP amplitude absolute value (SEP-amp) and the SEP amplitude side-to-side ratio (SEP-ratio).Clinical outcome at 3 months postoperatively was assessed using the modified Rankin scale (mRS-3M).ResultsThe positive predictive values (PPVs) for SEP-amp and SEP-ratio were 95.5% and 100%, respectively, with the negative predictive values (NPVs) being 60.0% and 100%, respectively. The SEP-ratio correlated fully with mRS-3M.ConclusionThe median SEP side-to-side N20/P25 amplitude ratio seems to be a very strong positive and negative predictor of the clinical outcome of urgent recanalization of an extracranial ICA occlusion.SignificanceThe results suggest that cortical evoked activity may help in selection patient for surgical recanalization and predict clinical recovery after an acute ischemic stroke.     

Measuring the effects of first antiepileptic medication in Temporal Lobe Epilepsy: Predictive value of quantitative-EEG analysis

ObjectiveTo determine the quantitative EEG responses in a population of drug-naïve patients with Temporal Lobe Epilepsy (TLE) after Levetiracetam (LEV) initiation as first antiepileptic drug (AED). We hypothesized that the outcome of AED treatment can be predicted from EEG data in patients with TLE.MethodsTwenty-three patients with TLE and twenty-five healthy controls were examined. Clinical outcome was dichotomized into seizure-free (SF) and non-seizure-free (NSF) after two years of LEV. EEG parameters were compared between healthy controls and patients with TLE at baseline (EEG^pre) and after three months of AED therapy (EEG^pre-post) and between SF and NSF patients. Receiver Operating Characteristic curves models were built to test whether EEG parameters predicted outcome.ResultsAED therapy induces an increase in EEG power for Alpha (p = 0.06) and a decrease in Theta (p < 0.05). Connectivity values were lower in SF compared to NSF patients (p < 0.001). Quantitative EEG predicted outcome after LEV treatment with an estimated accuracy varying from 65.2% to 91.3% (area under the curve [AUC] = 0.56–0.93) for EEG^pre and from 69.9% to 86.9% (AUC = 0.69–0.94) for EEG^pre-post.ConclusionsAED therapy induces EEG modifications in TLE patients, and such modifications are predictive of clinical outcome.SignificanceQuantitative EEG may help understanding the effect of AEDs in the central nervous system and offer new prognostic biomarkers for patients with epilepsy.     

Force decline after low and high intensity contractions in persons with multiple sclerosis

ObjectiveForce decline during strong contractions is dominated by changes in the periphery whereas during weaker contraction changes in voluntary activation become more important. We compared force decline and contributing factors in persons with multiple sclerosis (PwMS) during low and high intensity contractions.MethodsIndex finger abduction force, force evoked by electrical stimulation of the ulnar nerve at rest (RTw), and during MVCs were investigated in 19 PwMS and 19 controls. Participants performed contractions in sets of six contractions (7 s-on, 3 s-off) at 25% or 80% MVC. After each set, a 5 s-MVC was performed with superimposed nerve stimulation followed by RTw. Contractions were repeated until MVC dropped below 80% of initial MVC.ResultsLow compared to high intensity contractions caused a greater decline in voluntary activation and a smaller decline in RTw. Compared to controls, PwMS accomplished equal sets of contractions but showed a smaller decline in RTw. Female PwMS showed poorer voluntary activation. The number of low intensity contractions was associated with sense of fatigue in PwMS.ConclusionAlthough, no difference in fatigability was observed, the mechanism contributing to force decline differed between PwMS and controls during submaximal contractions.SignificanceDuring weak contractions, fatigue and fatigability are associated in PwMS.     

Sarcolemmal depolarization in sporadic inclusion body myositis assessed with muscle velocity recovery cycles

ObjectiveTo study patients with sporadic inclusion body myositis (sIBM) with muscle velocity recovery cycles (MVRC) to assess muscle membrane excitability, pathophysiological mechanisms and potential biomarkers of this disorder.MethodsMVRC were recorded from 20 individuals with sIBM from tibialis anterior (TA) and rectus femoris (RF) muscles. Excitability parameters were compared with MVRC data obtained from 22 normal controls >50 years.ResultsMuscle relative refractory period was prolonged in both TA (6.4 ms vs 4.4 ms, P < 0.001) and RF (7.1 ms vs 3.9 ms, P < 0.001) of sIBM affected muscle when compared to controls. Early supernormality was reduced in both TA (3.6% vs 8.8% P = 0.001) and in RF (mean 5.4% vs 13% P < 0.001). Late supernormality was only decreased significantly in sIBM affected TA (1.8% vs 3.6% P = 0.001) but not in RF. No consistent correlations between MVRC parameters and clinical markers of sIBM disease severity were found.ConclusionThe resting sarcolemmal muscle membrane potential of sIBM muscle is depolarized relative to that of normal controls, which may be related to intramuscular amyloid deposition in sIBM.SignificanceSarcolemmal depolarization may play a role in muscle dysfunction and weakness observed in sIBM patients.     

Inter-ictal network of focal epilepsy and effects of clinical factors on network activity

ObjectiveAim of the study was to explore the inter-ictal, resting-state EEG network in patients with focal epilepsy (FE) and to specify clinical factors that influence network activity.MethodsFunctional EEG connectivity (EEGfC) differences were computed between 232 FE patients (FE group) and 77 healthy controls. EEGfC was computed among 23 cortical regions within each hemisphere, for 25 very narrow bands from 1 to 25 Hz. We computed independent effects for six clinical factors on EEGfC in the FE group, by ANOVA and post-hoc t-statistics, corrected for multiple comparisons by false discovery rate method.ResultsRobust, statistically significant EEGfC differences emerged between the FE and the healthy control groups. Etiology, seizure type, duration of the illness and antiepileptic treatment were independent factors that influenced EEGfC. Statistically significant results occurred selectively in one or a few very narrow bands and outlined networks. Most abnormal EEGfC findings occurred at frequencies that mediate integrative and motor activities.ConclusionsFE patients have abnormal resting-state EEGfC network activity. Clinical factors significantly modify EEGfC.SignificanceDelineation of the FE network and modifying factors can open the way for targeted investigations and introduction of EEGfC into epilepsy research and practice.     

Electrodiagnostic findings in COVID-19 patients: A single center experience

ObjectiveNeurological manifestations in patients with coronavirus disease 2019 (COVID-19) have been reported from early features of anosmia and dysgeusia to widespread involvement of the central nervous system, peripheral nervous system, as well as the neuromuscular junction and muscle. Our study objective is to evaluate the electromyography and nerve conduction study (EMG/NCS) findings among COVID-19 patients and look for possible correlations.MethodsThis is a hospital-based retrospective observational study. All COVID-19 patients between the period of 1st January 2020 to 31st December 2020 undergoing an EMG/NCS were included.ResultsEighteen patients (12 male and 6 female) were included. Mean age was 55 ± 12 years. 11 patients required intubation for a mean period of 18.6 days (range: 3–37 days). Electrodiagnostic findings were consistent with a myopathy in a majority of these patients (82%). Five of them also had a concurrent axonal neuropathy. In the remaining patients who did not require intubation (n = 7), three patients had myopathic EMG changes and one had Guillain Barre syndrome.ConclusionAt this time, there are no neuromuscular-specific recommendations for patients who contract COVID-19. Only time and additional data will unveil the varying nature and potential neurological sequelae of COVID-19.SignificanceMyopathic EMG changes are commonly seen in critically ill COVID-19 patients, especially with a prolonged hospital stay.     

Retinal and optic nerve magnetic resonance diffusion-weighted imaging in acute non-arteritic central retinal artery occlusion

ObjectivesDiffusion weighted imaging hyperintensity (DWI-H) has been described in the retina and optic nerve during acute central retinal artery occlusion (CRAO). We aimed to determine whether DWI-H can be accurately identified on standard brain magnetic resonance imaging (MRI) in non-arteritic CRAO patients at two tertiary academic centers.Materials and methodsRetrospective cross-sectional study that included all consecutive adult patients with confirmed acute non-arteritic CRAO and brain MRI performed within 14 days of CRAO. At each center, two neuroradiologists masked to patient clinical data reviewed each MRI for DWI-H in the retina and optic nerve, first independently then together. Statistical analysis for inter-rater reliability and correlation with clinical data was performed.ResultsWe included 204 patients [mean age 67.9±14.6 years; 47.5% females; median time from CRAO to MRI 1 day (IQR 1-4.3); 1.5 T in 127/204 (62.3%) and 3.0 T in 77/204 (37.7%)]. Inter-rater reliability varied between centers (κ = 0.27 vs. κ = 0.65) and was better for retinal DWI-H. Miss and error rates significantly differed between neuroradiologists at each center. After consensus review, DWI-H was identified in 87/204 (42.6%) patients [miss rate 117/204 (57.4%) and error rate 11/87 (12.6%)]. Significantly more patients without DWI-H had good visual acuity at follow-up (p = 0.038).ConclusionsIn this real-world case series, differences in agreement and interpretation accuracy among neuroradiologists limited the role of DWI-H in diagnosing acute CRAO on standard MRI. DWI-H was identified in 42.6% of patients and was more accurately detected in the retina than in the optic nerve. Further studies are needed with standardized novel MRI protocols.     

Predictive factors for the development of epilepsy after ischemic stroke

ObjectivesIschemic stroke is one of the most common causes of epilepsy in adults. The incidence of post-stroke epilepsy (PSE) is approximately 7%. Risk factors are higher stroke severity, cortical localization, higher National Institute of Health Stroke Scale (NIHSS) upon admission and acute symptomatic seizures. We analyzed the predictive factors of PSE development in our population.Materials and methodsRetrospective observational cohort of adult patients (age ≥ 18 years) with ischemic stroke assessed between January 2012 and June 2020. Patients with personal history of epilepsy and potentially epileptogenic structural injury other than acute or chronic stroke were excluded. Demographic, clinical and imaging variables were evaluated in a multivariate analysis for independent risk factors associated with PSE.ResultsMedical records of 1586 stroke patients were reviewed, 691 met the inclusion criteria and had at least one year of follow-up. Of them, 428 (61.9%) were males. During follow-up, 6.2% had diagnosis of PSE (42/691) with a higher frequency of: previous ischemic stroke, higher NIHSS upon admission, treatment with rt-PA, higher Fazekas scale grade, cortical involvement, hemorrhagic transformation, acute symptomatic seizures, longer hospitalization and higher modified Rankin Scale (mRS) at discharge compared to the group without PSE. In a multivariate analysis, acute symptomatic seizures (OR=3.22, p: 0.033), cortical involvement (OR=0.274, p < 0.05), Fazekas scale score (OR=0.519, p < 0.05) and mRS at discharge (OR=1.33, p: 0.043) were independent risk factors.ConclusionsThe variables related to higher risk of PSE were similar to those reported in the literature, highlighting the importance of neuroimaging findings, acute symptomatic seizures during hospitalization and neurological deficit at discharge. The data obtained will serve as the basis for construction of predictive models, allowing to individualize PSE probability in our population.     

Gold Coast diagnostic criteria increase sensitivity in amyotrophic lateral sclerosis

ObjectiveThis study evaluates diagnostic accuracy of the proposed ‘Gold Coast’ (GC) diagnostic criteria for amyotrophic lateral sclerosis (ALS).MethodsFive European centres retrospectively sampled consecutive patients referred for electromyography on suspicion of ALS. Patients were classified according to the GC criteria, the revised El Escorial (rEE) criteria and the Awaji (AW) criteria without and with the ‘Possible’ category (+ Poss). Reference standard was ALS confirmed by disease progression at follow-up.ResultsOf 404 eligible patients 272 were diagnosed as ALS, 94 had mimicking disorders, 35 were lost for follow-up, and three had insufficient data. Sensitivity for the GC criteria was 88.2% (95% CI: 83.8-91.8%), which was higher than for previous criteria, of which the AW + Poss criteria reached the highest sensitivity of 77.6% (95% CI: 72.2–82.4%) (p < 0.001). Specificity was high for all criteria. The increase in sensitivity for the GC criteria was mainly due to the inclusion of 28 patients with progressive muscular atrophy (PMA).ConclusionsThe simpler GC criteria increase the sensitivity, primarily due to considering PMA as a form of ALS with high specificity preserved.SignificanceThis validation study supports that GC criteria should be used in clinical practice and may be used for inclusion in trials.     

Spectrum of PAH gene mutations and genotype-phenotype correlation in patients with phenylalanine hydroxylase deficiency from Shanxi province

BackgroundPhenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive inborn error that affects phenylalanine (Phe) metabolism. It has a complex phenotype with many variants and genotypes among different populations. Shanxi province is a high-prevalence area of PAHD in China.MethodsIn this study, eighty-nine PAHD patients were subjected to genetic testing using Sanger sequencing, followed by multiplex ligation-dependent probe amplification analysis (MLPA). Allelic and genotypic phenotype values (APV and GPV, respectively) were used for genotype-based phenotypic prediction.ResultsFifty-one types of variants, including three novel forms, were identified. The predominant variant was p.R243Q (22.09%), followed by p.R53H (10.47%), p.EX6-96A > G (9.30%), p.V399V (5.23%) and p.R413P (3.49%). Notably, mild hyperphenylalaninemia (MHP) has a high prevalence in this region (up to 45.76%), and the variant p.R53H was solely observed in patients of MHP. According to the genotype–phenotype prediction, the APV/GPV system was well correlated with the metabolic phenotype of most PAHD patients.ConclusionWe have systematically constructed the mutational and phenotypic spectrum of PAH in Shanxi province. Hence, this study will help to further understand the genotype-phenotype associations in PAHD patients, and it may offer more reliable genetic counseling and management.