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Objective: To determine genotype-phenotype correlation in succinic semialdehyde dehydrogenase (SSADH) deficiency., Methods: ALDH5A1 variants were studied with phenotype correlation in the SSADH natural history study. Assignment of gene variant pathogenicity was based on in silico testing and in vitro enzyme activity after site-directed mutagenesis and expression in HEK293 cells. Phenotypic scoring used a Clinical Severity Score (CSS) designed for the natural history study., Results: Twenty-four patients were enrolled (10 male, 14 female, median age 8.2 years). There were 24 ALDH5A1 variants, including 7 novel pathogenic variants: 2 missense, 3 splice site, and 2 frameshift. Four previously reported variants were identified in >5% of unrelated families. There was a correlation with age and presence ( p = 0.003) and severity ( p = 0.002) of epilepsy and with obsessive-compulsive disorder (OCD) ( p = 0.016). The median IQ score was 53 (Q25-Q75, 49-61). There was no overall correlation between the gene variants and the CSS, although a novel missense variant was associated with the mildest phenotype by CSS in the only patient with a normal IQ, whereas a previously reported variant was consistently associated with the most severe phenotype., Conclusions: Seven novel pathogenic and one previously unpublished benign ALDH5A1 variants were detected. There is an age-dependent association with worsening of epilepsy and presence of OCD in SSADH deficiency. Overall, there does not appear to be a correlation between genotype and phenotypic severity in this cohort of 24 patients. We did find a suspected correlation between a novel pathogenic missense variant and high functionality, and a previously reported pathogenic missense variant and maximal severity., (© 2020 American Academy of Neurology.)

Objective: To determine whether REM sleep without atonia (RSWA) during polysomnography (PSG) predicts phenoconversion in patients with idiopathic REM sleep behavior disorder (iRBD), a prodromal feature of a neurodegenerative disease., Methods: We analyzed RSWA in 60 patients with iRBD, including manual phasic, tonic, and any muscle activity in the submentalis and anterior tibialis muscles and the automated REM atonia index in the submentals. We identified patients who developed parkinsonism or mild cognitive impairment (MCI) during at least 3 years of follow-up after PSG. Kaplan-Meier analysis was performed and receiver operator curves were calculated to determine RSWA cutoffs predicting faster phenoconversion., Results: Twenty-six (43%) patients developed parkinsonism (n = 17) or MCI (n = 9). Phenoconverters were older at iRBD diagnosis ( p = 0.02). Median time to phenoconversion was 3.9 ± 2.5 years. iRBD phenoconverters had significantly more RSWA at diagnosis. Phenoconversion risk from iRBD diagnosis was 20% and 35% at 3 and 5 years, respectively, with greater risk in patients with iRBD with >46.4% any combined RSWA, which increased further to 30% and 55% at 3 and 5 years for patients >65 years of age at diagnosis., Conclusions: Patients with iRBD with higher amounts of polysomnographic RSWA had a greater risk of developing Parkinson disease or MCI. Patients with older age and higher RSWA amounts had more rapid phenoconversion than younger patients with RBD. Our study suggests that RSWA is a potential biomarker for risk stratification of iRBD phenoconversion that could facilitate prognostication for patients with iRBD., Classification of Evidence: This study provides Class II evidence that for patients with iRBD, increased RSWA correlates with increased risk for developing parkinsonism or MCI., (© 2019 American Academy of Neurology.)

Objective: To identify the genetic and physiologic basis for recessive myasthenic congenital myopathy in 2 families, suggestive of a channelopathy involving the sodium channel gene, SCN4A ., Methods: A combination of whole exome sequencing and targeted mutation analysis, followed by voltage-clamp studies of mutant sodium channels expressed in fibroblasts (HEK cells) and Xenopus oocytes., Results: Missense mutations of the same residue in the skeletal muscle sodium channel, R1460 of Na V 1.4, were identified in a family and a single patient of Finnish origin (p.R1460Q) and a proband in the United States (p.R1460W). Congenital hypotonia, breathing difficulties, bulbar weakness, and fatigability had recessive inheritance (homozygous p.R1460W or compound heterozygous p.R1460Q and p.R1059X), whereas carriers were either asymptomatic (p.R1460W) or had myotonia (p.R1460Q). Sodium currents conducted by mutant channels showed unusual mixed defects with both loss-of-function (reduced amplitude, hyperpolarized shift of inactivation) and gain-of-function (slower entry and faster recovery from inactivation) changes., Conclusions: Novel mutations in families with myasthenic congenital myopathy have been identified at p.R1460 of the sodium channel. Recessive inheritance, with experimentally established loss-of-function, is a consistent feature of sodium channel based myasthenia, whereas the mixed gain of function for p.R1460 may also cause susceptibility to myotonia., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: Children with trunk hypotonia may have limited ability to maintain an upright weight-bearing position, resulting in decreased postural control and a delay in achieving gross motor milestones., Purpose: The purpose of this case series is to report the effect of a home-based dynamic standing program on postural control and gross motor activity in 2 children with trunk hypotonia., Descriptions: Child 1 (aged 24 months, Gross Motor Function Classification Scale Level IV) and Child 2 (aged 21 months, Gross Motor Function Classification Scale Level V) participated in a standing program using the Upsee harness at home 3 days per week for 12 weeks., Outcomes: Both children improved their gross motor function, and Child 1 demonstrated improved trunk control in sitting., What This Case Adds: The use of the Upsee harness was an effective intervention for these children with trunk hypotonia to achieve weight-bearing and improve gross motor abilities.

Purpose: To study the relationship between central hypotonia and motor development, and to determine the relative contribution of nuchal, truncal, and appendicular hypotonia domains to motor development., Methods: Appendicular, nuchal, and truncal tones of high-risk infants were assessed, as was their psychomotor developmental index (PDI). Infants with peripheral hypotonia were excluded., Results: We included 164 infants (mean age 9.6 ± 4 months), 36 with normal tone in all 3 domains and 128 with central hypotonia. Twenty-six of the latter had hypotonia in 1 domain and 102 had multiple combinations of 3 domains. Hypotonia domains were distributed as follows: truncal (n = 115), appendicular (n = 93), and nuchal (n = 70). Each domain was significantly associated with PDI scores (P < .001) but not with a later diagnosis of cerebral palsy. On linear regression, nuchal hypotonia had the strongest contribution to PDI scores (β = -0.6 [nuchal], -0.45 [appendicular], and -0.4 [truncal], P < .001)., Conclusions: Central hypotonia, especially nuchal tone, is associated with lowered motor development scores.

Purpose: To study the relationship between eyelid laxity and ocular symptoms and signs of dry eye (DE)., Methods: A total of 138 patients with normal external anatomy were prospectively recruited from a Veterans Administration hospital. Symptoms (via the Dry Eye Questionnaire 5 and Ocular Surface Disease Index) and signs of DE were assessed along with presence or absence of eyelid laxity., Results: It was observed that 71% of participants (n = 98) had clinical evidence of eyelid laxity (upper and/or lower) compared with 29% (n = 40) with no eyelid laxity. Individuals with eyelid laxity were older (67 ± 10 vs. 55 ± 8 years without laxity, P < 0.005) and more frequently male (76% of males had laxity vs. 18% females, P < 0.005). Patients with eyelid laxity had increased symptoms and signs of DE compared with their counterparts without laxity including ocular pain described as grittiness (63% vs. 45%, P = 0.049), decreased tear break-up time (8.6 ± 3 vs. 10.3 ± 4 seconds, P = 0.02), increased corneal staining (2.5 ± 3 vs. 1 ± 2, P = 0.002), decreased Schirmer score (14±6 vs. 17±7 mm, P = 0.01), increased meibomian gland drop out (2 ± 1 vs. 0.8 ± 0.8, P < 0.005), increased eyelid vascularity (0.8 ± 0.8 vs. 0.2 ± 0.5, P < 0.005), and more abnormal meibum quality (2 ± 1.3 vs. 1.4 ± 1.2, P = 0.02). In a multivariable analysis considering both signs of DE and laxity, lower eyelid laxity remained significantly associated with ocular surface disease index scores, suggesting a direct effect of laxity on symptoms of DE., Conclusions: The presence of eyelid laxity associates with abnormal tear parameters compared with the absence of eyelid laxity. Based on these data, it is important for clinicians to test for eyelid laxity in patients with symptoms and/or signs of DE.

Purpose: To determine corneal biomechanical properties in patients with floppy eyelid syndrome (FES) and to compare them with eyes of controls., Methods: This case-control study included 208 eyes (72 eyes with FES and 136 without FES) of 107 patients (37 patients with FES and 70 without FES). Patients underwent a complete clinical eye examination that included corneal biomechanical evaluation carried out with the Reichert Ocular Response Analyzer., Results: Corneal hysteresis (CH), corneal resistance factor (CRF), central corneal thickness (CCT), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc) were evaluated. Mean CH was significantly lower in patients with FES than in those without FES (9.51 ± 1.56 vs. 11.66 ± 9.11; P < 0.001). These results remained statistically significant after adjusting for age and apnea-hypoapnea index (AHI) (P = 0.028). Mean CRF was 10.02 ± 2.08 in the group of patients with FES and 11.21 ± 5.36 in the group of patients without FES (P = 0.001). Mean IOPcc was 17.7 ± 4.8 in patients with FES and 16.3 ± 4.4 in those without FES (P = 0.036). After adjusting for age and AHI, these differences in CRF and IOPcc were not statistically significant (P = 0.26 and P = 0.87, respectively). No statistically significant difference was found between patients with and without FES for Goldmann-correlated intraocular pressure or CCT., Conclusions: Patients with FES had statistically lower CH values. Our findings suggest that corneal biomechanical properties could be changed in patients with FES, reflecting additional structural changes in FES.

Objective: The objective of this cross-sectional study was to test the hypothesis that patients with Parkinson disease (PD) and freezing of gait (PD+FOG) would demonstrate sleep disturbances comparable to those seen in patients with REM sleep behavior disorder (RBD) and these changes would be significantly different from those in PD patients without FOG (PD-FOG) and age-matched controls., Methods: We conducted overnight polysomnography studies in 4 groups of subjects: RBD, PD-FOG, PD+FOG, and controls. Tonic and phasic muscle activity during REM sleep were quantified using EMG recordings from the chin, compared among study groups, and correlated with disease metrics., Results: There were no significant differences in measures of disease severity, duration, or dopaminergic medications between the PD+FOG and PD-FOG groups. Tonic muscle activity was increased significantly (p < 0.007) in the RBD and PD+FOG groups compared to the PD-FOG and control groups. There was no significant difference in tonic EMG between the PD+FOG and RBD group (p = 0.364), or in tonic or phasic EMG between the PD-FOG and control group (p = 0.107). Phasic muscle activity was significantly increased in the RBD group compared to all other groups (p = 0.029) and between the PD+FOG and control group (p = 0.001), but not between the PD+FOG and PD-FOG groups (p = 0.059)., Conclusions: These findings provide evidence that increased muscle activity during REM sleep is a comorbid feature of patients with PD who exhibit FOG as a motor manifestation of their disease.

Purpose: The association between floppy eyelid syndrome and keratoconus (KCN) has been well established, but the converse relationship has not yet been examined and is the objective of this study. The study also investigates the prevalence of obesity and obstructive sleep apnea (OSA) in KCN patients., Methods: A prospective case-control study of KCN patients with age-, sex-, race-, and body mass index-matched controls was conducted at the Ross Eye Institute, Buffalo, NY. Fifteen patients were enrolled in each group. Extensive eyelid laxity measurements were performed on both groups. Complete medical/ophthalmic history and Epworth Sleepiness Scales were completed on 50 KCN patients and were compared with the normal population., Results: Increased eyelid measurements of the vertical lid pull, lower lid pull, medial canthal tendon distraction, and palpebral width were found in the KCN group compared with the matched control group (P = 0.001, 0.005, 0.04, and 0.01, respectively), and a more rubbery tarsus (P = 0.03), increased corneal diameter (P = 0.02), and increased exophthalmometry measurements (P = 0.01) were also found. The prevalence of OSA (24%, 14/50) and obesity (52%, 26/50) were higher in the KCN patients versus the normal population., Conclusions: KCN patients have increased laxity to their eyelids, along with a more rubbery tarsus, which may be along the spectrum of floppy eyelid syndrome. KCN patients had a high prevalence of OSA and obesity. The high prevalence of OSA in KCN patients is an important association that carries an increased risk of death from any cause and stroke.

Background and Purpose: The pattern of antenatal brain injury varies with gestational age at the time of insult. Deep brain nuclei are often injured at older gestational ages. Having previously shown postnatal hypertonia after preterm fetal rabbit hypoxia-ischemia, the objective of this study was to investigate the causal relationship between the dynamic regional pattern of brain injury on MRI and the evolution of muscle tone in the near-term rabbit fetus., Methods: Serial MRI was performed on New Zealand white rabbit fetuses to determine equipotency of fetal hypoxia-ischemia during uterine ischemia comparing 29 days gestation (E29, 92% gestation) with E22 and E25. E29 postnatal kits at 4, 24, and 72 hours after hypoxia-ischemia underwent T2- and diffusion-weighted imaging. Quantitative assessments of tone were made serially using a torque apparatus in addition to clinical assessments., Results: Based on the brain apparent diffusion coefficient, 32 minutes of uterine ischemia was selected for E29 fetuses. At E30, 58% of the survivors manifested hind limb hypotonia. By E32, 71% of the hypotonic kits developed dystonic hypertonia. Marked and persistent apparent diffusion coefficient reduction in the basal ganglia, thalamus, and brain stem was predictive of these motor deficits., Conclusions: MRI observation of deep brain injury 6 to 24 hours after near-term hypoxia-ischemia predicts dystonic hypertonia postnatally. Torque-displacement measurements indicate that motor deficits in rabbits progressed from initial hypotonia to hypertonia, similar to human cerebral palsy, but in a compressed timeframe. The presence of deep brain injury and quantitative shift from hypo- to hypertonia may identify patients at risk for developing cerebral palsy.

Objective: Utilizing a population-based registry, the burden of comorbidity was ascertained in a sample of children with cerebral palsy and stratified according to both neurologic subtype and functional capability with respect to gross motor skills., Methods: The Quebec Cerebral Palsy Registry was utilized to identify children over a 4-year birth interval (1999-2002 inclusive) with cerebral palsy. Information on neurologic subtype classified according to the qualitative nature and topographic distribution of the motor impairment on neurologic examination, Gross Motor Function Classification System (GMFCS) categorization of motor skills, and the presence of certain comorbidities (cortical blindness, auditory limitations, nonverbal communication skills, gavage feeding status, and coexisting afebrile seizures in the prior 12 months) was obtained., Results: The frequency of individual comorbidities, their proportional distribution, and mean number of occurrences basically falls into a significant dichotomous distribution. Across the spectrum of comorbidities considered, these comorbidities are relatively infrequently encountered in those with spastic hemiplegic or spastic diplegic variants or ambulatory GMFCS status (levels I-III), while these entities occur at a frequent level for those with spastic quadriplegic, dyskinetic, or ataxic-hypotonic variants or nonambulatory GMFCS status (levels IV and V)., Conclusion: The enhanced burdens of comorbidity are unevenly distributed in children with cerebral palsy in a manner that can be associated with either a specific neurologic subtype (spastic quadriplegic, dyskinetic, ataxic-hypotonic) or nonambulatory motor status (Gross Motor Function Classification System levels IV and V). This provides enhanced value to the utilization of these classification approaches.

Study Design: Case-control study., Objective: To evaluate respiratory muscle force in children with myelomeningocele., Summary of Background Data: Myelomeningocele is a common spinal cord malformation with limitations linked to central nervous system lesions and abnormalities in respiratory movements. Despite this, little attention has been given to evaluating respiratory muscle force in these patients., Methods: Children with myelomeningocele aged between 4 and 14 years (myelomeningocele group; MG, n = 20) were studied and compared with healthy children (control group; CG, n = 20) matched for age and gender. Respiratory muscular force was evaluated by maximum inspiratory (Pimax) and expiratory (Pemax) pressures., Results: Groups were similar for age [CG = 8 (6-13) x MG = 8 (4-14), P > 0.05]; gender, and body mass index [CG = 17.4 (14.1-24.7) x MG = 19.2 (12.6-31.9), P > 0.05]. The lumbosacral region was predominantly affected (45%). Maximum respiratory pressures were significantly higher in CG than MG (Pimax = CG: -83 +/- 21.75 > MG: -54.1 +/- 23.66; P < 0.001 and Pemax = CG: +87.4 +/- 26.28 > MG: +64.6 +/- 26.97; P = 0.01). Patients with upper spinal lesion (UL) had lower maximum respiratory pressure values than those with lower spinal lesion (LL), [Pimax (UL = -38.33 +/- 11.20 cm H2O x LL = -60.85 +/- 24.62 cm H2O), P < 0.041 and Pemax (UL = +48 +/- 20.82 cm H2O x LL + 71.71 +/- 26.73 cm H2O), P = 0.067])., Conclusion: Children with myelomeningocele at the ages studied presented reduced respiratory muscle force with more compromise in upper spinal lesion.

Purpose: To describe the outcomes of children diagnosed before the age of two with idiopathic hypotonia., Methods: A total of 105 parents of children who were diagnosed with hypotonia returned a questionnaire. Medical records were reviewed., Results: A transient impairment group (10.5%) reported no problems. A minimal impairment group (32.4%) had mild problems such as learning disability or language delay but no major developmental diagnosis. A globally impaired group (40.9%) had mental retardation or a recognizable genetic/developmental diagnosis. More than 50% of the minimal impairment group had poor coordination, language delay, and learning difficulties. The mean walking age (minimal group) was 22 months. Initial fine motor and cognitive, but not gross motor, developmental quotients were significantly greater in the minimal compared with global impairment group., Conclusion: Deficits in motor coordination, language, and learning difficulties were common problems that persisted in the minimal and global impairment groups.

Purpose: This study extended previous work on defining characteristics of children with hypotonia., Methods: A survey regarding previously identified characteristics of hypotonia, examination tools, interventions, and prognosis was sent to a random sample of 500 physical therapists and 500 occupational therapists., Results: A total of 268 surveys were returned, for a response rate of 26.8%. Characteristics most frequently observed in children with hypotonia included decreased strength, hypermobile joints, and increased flexibility. Observation was the most commonly cited assessment tool and 85% of those surveyed believe that characteristics of hypotonia improve with therapy., Conclusions: Despite agreement among physical and occupational therapists on characteristics of hypotonia and potential for improvement, clear clinical guidelines for the diagnosis and quantification of hypotonia have yet to be determined. Research is needed to develop an operational definition of hypotonia, develop valid tests and assess effectiveness of intervention.

We describe a case of West Nile virus (WNV) infection in an HIV-infected patient who presented with an isolated flaccid monoparesis of the right upper extremity. To our knowledge, this is the first reported case of flaccid paralysis caused by WNV infection in an HIV-infected patient. We then review the medical literature on WNV infection occurring among patients who are infected with HIV. Unlike most of the cases reported in the literature, our patient had partial recovery of his neurologic deficits.

Objective: To describe the disease course and natural history of Type A Niemann-Pick disease (NPD)., Methods: Ten patients with NPD-A (six male, four female; age range at entry: 3 to 6 months) were serially evaluated including clinical neurologic, ophthalmologic, and physical examinations, and assessment of development. Laboratory analyses, abdominal and brain ultrasounds, and chest radiographs also were obtained and information on intercurrent illnesses and cause of mortality was collected., Results: All affected infants had a normal neonatal course and early development. The first symptom detected in all patients was hepatosplenomegaly. Developmental age did not progress beyond 10 months for adaptive behavior, 12 months for expressive language, 9 months for gross motor skills, and 10 months for fine motor skills. Non-neurologic symptoms included frequent vomiting, failure to thrive, respiratory infections, irritability, and sleep disturbance. Neurologic examination at the time of presentation was normal in most patients. Later neurologic examinations revealed progressive hypotonia with loss of the deep tendon reflexes. All patients had cherry red spots by 12 months. The median time from diagnosis to death was 21 months. The cause of death was respiratory failure in nine patients and complications from bleeding in the tenth., Conclusions: The clinical course in Type A Niemann-Pick disease is similar among affected patients and is characterized by a relentless neurodegenerative course that leads to death, usually within 3 years.

Purpose of Review: There is currently intense interest in understanding why certain elderly individuals become frail and disabled with age whereas others do not. Is frailty the result of an acceleration of normal aging processes or is it the result of chronic medical conditions that are superimposed on the conventional mechanisms of aging? The clinical problem of falls has long been recognized as a threat to some elderly individuals, but too often is not considered worthy of objective study. The factors underlying falls are now being investigated as part of the increasing attention being paid to the evolution of frailty in the elderly., Recent Findings: Frailty in the elderly has been given many names, but increasing efforts are now being made to define frailty in a standardized way that would allow more objective study. The frail elderly patient usually shows loss of both neurological and muscle function. Falls in the elderly are an example in which deterioration may be present in both functions. Methods are being developed to separate the loss of muscle capacity from the associated loss of central and peripheral neurological function involved in gait and balance., Summary: The definition of frailty has been centered around the onset of accelerated weight loss with an associated decrease of mass and strength of skeletal muscle. New studies are discussed that extend this definition. Methods for a more detailed analysis of the physiological and metabolic deficits leading to falls in the elderly may provide a better understanding of frailty in general.

Background: In the last few years, rare cases of acute quadriplegic myopathy (AQM*) with myosin-deficient muscle fibres occurring after solid organ transplantation has been reported. The aim of the present study was to review all cases of AQM with myosin deficient fibres seen at our institution among a large series of patients after orthotopic liver transplants (OLT), with special attention to clinical aspects and associated risk factors. Additionally, an extensive review of all ultrastructurally demonstrated cases of AQM in transplant recipients is also included., Patients and Methods: Among patients involved in 281 consecutive liver transplant procedures performed in a 4-year period, 3 men and 1 woman developed an arreflexic, flaccid quadriplegia in the immediate postoperative period of OLT. After ruling out other causes of weakness, a muscle biopsy was performed and a loss of thick (myosin) filaments was confirmed by ultrastructural analysis in all cases. Accurate clinical, epidemiological, and evolutive data were recorded., Results: Corticosteroids had been used at usual dosage given to liver transplant recipients; all four patients had several intra- and postoperative complications leading to receiving significantly higher amounts of hemoderivates, to develop renal failure in all cases, and to require a significantly higher number of reoperations within a few days after transplantation than our contemporaneous global series of liver transplant recipients. AQM patients required a significantly longer intensive care unit and hospital stay. Muscular recovery was the rule, but currently a mild myopathic gait remains in three patients. These and other reported cases of AQM do not histologically and clinically differ from AQM seen in other critically ill patients who have not had transplants., Conclusions: Patients with a complicated intra- and postoperative course of OLT who develop newly acquired acute muscle weakness should be suspected as having acute AQM with myosin-deficient muscle fibres. In this setting, differential diagnosis with other causes of weakness should be carried out, because the prognosis of this myopathy is good with early muscle rehabilitation therapy.

Background and Purpose: We used a rat model of reversible spinal ischemia to assess the effect of spinal cord temperature on the development of neurological and histopathologic changes after 20 minutes of reversible aortic occlusion. Spinal cord blood flow and CO2 reactivity was tested by using laser Doppler before and 60 minutes after ischemia., Methods: In halothane (1%)-anesthetized rats, the spinal cord temperature as assessed by using thermocouple in the paraspinal muscles was lowered to 34 degrees, 31 degrees, or 27 degrees C. After ischemia, spinal cord temperature was raised to 37 degrees C for the next 30 minutes. Animals were maintained in this normothermic condition for 8 hours, after which motor and sensory function were assessed. All animals were then anesthetized and perfused with 10% formalin for light microscopic analysis of spinal cords., Results: In normothermic animals, 20 minutes of ischemia resulted in a loss of CO2 reactivity and hind limb paraplegia with an attendant allodynia that persisted for the 8 hours of reperfusion. Even mild (34 degrees C) hypothermia resulted in significant improvement of neurological function compared with the normothermic group. In paraplegic animals, lumbosacral interneuronal pools localized primarily in laminae III through VII displayed heavy argyrophilic neurons and areas of localized necrosis. In moderate and deep hypothermic animals preservation of CO2 responsivity and complete recovery of neurological function were seen with no detectable histopathologic changes., Conclusions: These results show that a slight decrease in spinal cord temperature in the peri-ischemic period provides significant protection as measured by histopathology and neurological function.

We report four children with unusual facial features including severe blepharophimosis, ptosis, and a distinctive nose with a broad flat tip and a depressed bridge. All four patients were markedly hypotonic and had severe feeding difficulties and developmental delay. Two had congenital heart defects and all three who survived had hypoplastic teeth. Both of the male patients had cryptorchidism. These four children have a distinctive syndrome which is similar to that reported by Biesecker (J Med Genet (1991) 28: 131-134).

Clinical and neuropathologic observations after cervical spinal cord injury suggest varying involvement of gray and white matter. The resulting upper limb weakness may reflect varying degrees of upper motoneuron (UMN) and/or lower motoneuron (LMN) involvement. This study uses electrophysiologic measures, including compound muscle action potential (M response) amplitude, root mean square (RMS) of the surface electromyographic activity during voluntary muscle contractions and the firing rate of motor units, to distinguish UMN and LMN weakness in upper extremities after acute quadriplegia. M response amplitude did not correlate with strength; many muscles had large M responses given their strength. These muscles manifest: (1) high M/RMS ratios (ratio of electrically elicited to voluntarily recruited electromyographic activity) and (2) slow firing rates of single motor units during maximal isometric contractions. For muscles with normal M amplitudes, M/RMS ratio correlates inversely with strength. For muscles with normal M/RMS ratios, M amplitude correlates positively with strength. Cluster analysis was used to distinguish UMN, LMN or Mixed types of weakness. Distinguishing these different types of weakness in acute quadriplegia may allow individualized rehabilitation for the type of weakness present.

Seventeen children with spinal cord injuries that occurred before the age of 9 years were followed at the Alfred I. duPont Institute for a mean of 13.2 years (range 3-32 years). Fourteen of these patients (82%) developed subluxation or dislocation in one or both hips. Patients with spastic spinal cord injury (SCI) developed hip flexion and adduction contractures and had symptoms that tended to mimic those of cerebral palsy. Patients with flaccid SCI mirrored the "flail" hips of myelomeningocele. Pelvic obliquity occurred in spastic and flaccid children. Only one patient developed pain, and three had deformities suggesting avascular necrosis of the femoral head. At final follow-up, no patient had physical problems relating to the hip dysplasia.

A group of 86 women with genuine stress incontinence who underwent retropubic urethropexy were evaluated with both pre- and postoperative urodynamics. Twenty of these 86 women (23.3%) also had unstable detrusors preoperatively. Eleven of these 20 women (55%) had stable detrusors after retropubic urethropexy. Five of the 66 patients (7.6%) who had stable detrusors preoperatively were found to have unstable detrusors on postoperative urethrocystometry. The overall cure rate for women with detrusor instability and genuine stress incontinence was only 30%. Analysis of symptoms, previous anti-incontinence procedures, age, parity, and cystometric parameters revealed no differences between those women who had stable detrusors after retropubic urethropexy and those who remained unstable. Similarly, patients whose bladders became unstable after retropubic urethropexy could not be distinguished from those who remained stable. Patients undergoing retropubic urethropexy should understand the possibility that the operation may cause urinary incontinence due to detrusor instability even if it cures their genuine stress incontinence, and that if they have both genuine stress incontinence and detrusor instability, their chances for an operative cure of both conditions are low.

Retraction of the lower eyelid is a useful sign of disease. It is an early manifestation of weakness of the facial muscles, occurring with myopathies, myasthenia, and upper and lower motor neuron facial paresis. Rarely, lower and upper lid retraction occur without proptosis in patients with Graves disease. Lower lid retraction occurs in proptosis and varies directly with the degree of proptosis. It is also seen with senile entropion or ectropion, after eye muscle or orbital surgery, and with contraction of lid tissues. Apparent retraction results when the contralateral lower lid is pathologically elevated, as in Horner syndrome, in enophthalmos, or with vertical deviations of the eye.

Muscle tone develops in a orderly sequence through gestation and continues to change after birth. Hypotonia is frequently found in infants, and pathological degrees must be differentiated from normal variations. This distinction is possible if the clinician understands how muscle tone is regulated and modifies his examination to include some special clinical signs. A variety of pathological conditions can influence muscle tone, and hypotonia can be an early and valuable clue to recognizing neuromuscular, CNS, metabolic, and other disease states in this age group.