N. van Alfen

Neuralgic amyotrophy and hepatitis E virus infection

Objective: To determine whether there is an association between an acute preceding hepatitis E virus (HEV) infection and neuralgic amyotrophy (NA), and if so, whether patients with HEV-related NA differ from patients without an associated HEV infection. Methods: HEV testing was conducted in a retrospective cohort of 28 Cornish patients with NA (2011–2013) and a prospective cohort of 38 consecutive Dutch patients with NA (2004–2007). Acute-phase serum samples were analyzed for the presence of anti-HEV immunoglobulin (Ig) M and IgG and HEV RNA (quantitative real-time PCR). Results: Five cases (10.6%) of acute hepatitis E infection were identified in a total group of 47 patients with NA of whom serum samples were available. In 4 patients, HEV RNA was detected in serum samples taken at presentation. All patients with HEV-associated NA had clinical and electrophysiologic evidence of bilateral brachial plexus involvement. Anti-HEV IgM positivity was not related to age, sex, disease severity, disease course, or outcome. Conclusions: Acute hepatitis E is found in 10% of patients with NA from the United Kingdom and the Netherlands. Further research is required to investigate the role of HEV in NA in other geographical locations and to determine pathophysiologic mechanisms.

Identifying deficits in balance control following vestibular or proprioceptive loss using posturographic analysis of stance tasks

OBJECTIVE To distinguish between normal and deficient balance control due to vestibular loss (VL) or proprioceptive loss (PL) using pelvis and shoulder sway measures. METHODS Body-worn gyroscopes measured pelvis and shoulder sway in pitch (anterior-posterior) and roll (side-to-side) directions in 6 VL, 6 PL and 26 control subjects during 4 stance tasks. Sway amplitudes were compared between groups, and were used to select optimal measures that could distinguish between these groups. RESULTS VL and PL patients had greater sway amplitudes than controls when standing on foam with eyes closed. PL patients also swayed more when standing with eyes closed on firm support and eyes open on foam. Standard sensory analysis techniques only differentiated VL patients from controls. Stepwise discriminate analysis showed that differentiation required pitch measures for VL patients, roll measures for PL patients, and both measures for all three groups. Pelvis measures yielded better discrimination than shoulder measures. CONCLUSIONS Distinguishing between normal and deficient balance control due to VL or PL required pitch and roll pelvis sway measures. SIGNIFICANCE Accurate identification of balance deficits due to VL or PL may be useful in clinical practice as a functional diagnostic tool or to monitor balance improvements in VL or PL patients.

Evaluation of prednisolone treatment in the acute phase of neuralgic amyotrophy: an observational study.

Background: Effective treatment for neuralgic amyotrophy (NA), a disabling brachial plexus syndrome of supposed immunomediated origin, is currently lacking. Given the circumstantial evidence of a beneficial effect of prednisolone on pain and paresis, this report evaluates the effects of prednisolone treatment administered in the acute phase in a retrospective case series of 50 NA patients. Methods: Baseline variables (eg, age, sex, type of NA and number of attacks), treatment variables (eg, time until treatment, regimen and use of analgesics) and outcome measures (eg, duration and severity of pain, time course and severity of paresis and functional outcome) were statistically analysed and compared with a historical control group of 203 untreated NA patients. Results: The baseline characteristics of the two patient groups were comparable. The median time until initial pain relief was lower in the study group (12.5 days vs 20.5 days), and a significantly higher percentage already recovered strength in the first month of treatment (18% vs 6.3%; p = 0.011). Twelve per cent had fully recovered within 1 year, while this was 1% for the controls (p<0.001), with the proportion reporting a “good” 12-month outcome also being higher (44% vs 10.7%; p<0.001). Side effects were reported by 20%, but none led to a discontinuation of treatment. Conclusion: Oral prednisolone seems effective in the acute phase of neuralgic amyotrophy with the current results supporting previous case reports. A regimen of oral prednisolone is therefore recommended in the acute phase of the syndrome pending a prospective, randomised trial verifying the results obtained.

Congenital myopathy caused by a novel missense mutation in the CFL2 gene

Nemaline myopathy and myofibrillar myopathy are heterogeneous myopathies that both comprise early-onset forms. We present two sisters from a consanguineous Iraqi Kurdish family with predominant axial and limb girdle weakness. Muscle biopsies showed features of both nemaline myopathy and myofibrillar myopathy. We performed homozygosity mapping in both siblings using an Affymetrix 250K Nspl SNP array. One of the overlapping homozygous regions harbored the gene CFL2. Because a mutation in CFL2 was identified in a family with nemaline myopathy, we performed sequence analysis of the gene and a novel homozygous missense mutation in exon 2 (c.19G>A, p.Val7Met) of CFL2 was identified in both siblings. CFL2 encodes the protein cofilin-2, which plays an important role in regulation of sarcomeric actin filaments. To our knowledge, this is the second family in which a mutation in CFL2 causes an autosomal recessive form of congenital myopathy with features of both nemaline and myofibrillar myopathy. Given the clinical variability and the multitude of histological features of congenital myopathies, CFL2 sequence analysis should be considered in patients presenting with an autosomal recessive form of congenital myopathy.

Vestibular and proprioceptive influences on trunk movements during quiet standing

We characterized upper trunk and pelvis motion in normal subjects and in subjects with vestibular or proprioceptive loss, to document upper body movement modes in the pitch and roll planes during quiet stance. Six bilateral vestibular loss (VL), six bilateral lower-leg proprioceptive loss (PL) and 28 healthy subjects performed four stance tasks: standing on firm or foam surface with eyes open or closed. Motion of the upper body was measured using two pairs of body-worn gyroscopes, one mounted at the pelvis and the other pair at the shoulders. Pitch and roll angular velocities recorded from the gyroscopes were analyzed separately for low-frequency (<0.7 Hz) and high-frequency (>3 Hz) motion. Low-frequency pitch motion was similar for all groups, consisting of in-phase pelvis and shoulder motion. High-frequency pitch motion in controls and VL subjects was dominated by pelvis motion with little shoulder motion, but vice versa in PL subjects. Low-frequency roll motion changed for all groups from mainly shoulder and little pelvis motion to in-phase pelvis and shoulder motion after moving from a firm to foam surface. In contrast, high-frequency roll motion changed from mainly shoulder motion to mainly pelvis motion with the change to a foam surface, except for PL subjects with eyes closed. Coherent low-frequency sway between pelvis and shoulder was only pronounced in VL patients. These results indicate that relative motion between the pelvis and shoulder depends on the support surface, the type of sensory loss, and whether the motion is in roll or pitch plane. Furthermore, relative motion between the pelvis and upper trunk is an integral part of movement modes used to control quiet stance. Vestibular loss patients showed very similar movement modes as controls, with larger amplitudes. Proprioceptive loss patients, however, used more shoulder motion and stabilized the pelvis for the high-frequency mode. We conclude that there is relative motion between the upper trunk and pelvis during quiet stance and suggest that it may contribute to balance control.

Sensory nerve conduction studies in neuralgic amyotrophy.

van Alfen N, Huisman WJ, Overeem S, van Engelen BGM, Zwarts MJ: Sensory nerve conduction studies in neuralgic amyotrophy. Neuralgic amyotrophy is a painful, episodic peripheral nerve disorder localized to the brachial plexus. Sensory symptoms occur in 80% of the patients. We assessed the frequency of abnormalities in sensory nerve conduction studies of the lateral and medial antebrachial cutaneous, radial sensory, median sensory, and ulnar sensory nerves in 112 patients. Sensory nerve conduction studies showed abnormalities in <20% of nerves, even when the nerve was clinically affected. The lateral and medial antebrachial cutaneous nerves were most often abnormal, in 15% and 17% of nerves. No correlation with the presence or localization of clinical deficits was found. Brachial plexus sensory nerve conduction studies seem to be of little diagnostic value in neuralgic amyotrophy. Our findings also indicate that some sensory lesions may be in the nerve roots instead of the plexus. An examination of normal sensory nerve conduction studies does not preclude neuralgic amyotrophy as a diagnosis.

Myopathy in a 20‐year‐old female patient with D4ST‐1 deficient Ehlers‐Danlos syndrome due to a homozygous CHST14 mutation

We here report on a 20‐year‐old female patient with EDS due to a homozygous CHST14 single nucleotide deletion resulting in D4ST‐1 deficiency, accompanied by muscle hypoplasia and muscle weakness. Findings of muscle ultrasound, electromyography, and muscle biopsy pointed to a myopathy, similarly as in other EDS types. This myopathy probably contributes to the gross motor developmental delay in this type of EDS.

Neuromuscular features in Marfan syndrome.

Marfan syndrome is a clinically and allelic heterogeneous, heritable connective tissue disorder with infrequently reported neuromuscular features. This study is the first to delineate these symptoms in a non‐selected population. Neuromuscular involvement was evaluated in 10 Marfan patients through a standardized questionnaire, physical examination, nerve conduction study (NCS), needle electromyography (EMG), muscle ultrasound, laboratory investigation, and muscle biopsy. Existing neuroimages were screened for dural ectasia and spinal meningeal cysts. Twenty healthy controls with similar age distribution completed the questionnaire.

Lumbosacral plexus neuropathy: a case report and review of the literature

Lumbosacral plexus neuropathy (LSPN) is an idiopathic clinical syndrome characterized by the sudden onset of neuropathic pain, followed by weakness and sometimes sensory disturbances in the distribution of the lumbosacral plexus. Prognosis is usually favourable, although complete recovery may take several months to years. LSPN is the lumbosacral counterpart of the neuralgic amyotrophy syndrome (idiopathic brachial plexus neuropathy). We present a patient who initially was misdiagnosed with a radicular syndrome, but illustrates the typical signs and symptoms of LSPN. We also give clinical and electromyographical criteria for the diagnosis of LSPN and review the literature.

Health-Related Quality of Life and Its Relation to Disease Severity in Boys With Duchenne Muscular Dystrophy Satisfied Boys, Worrying Parents—A Case-Control Study

The progression of Duchenne muscular dystrophy is expected to negatively influence the patients’ health-related quality of life, but knowledge of the relationship with disease severity is limited. We investigated the relationship between health-related quality of life (KIDSCREEN-52 questionnaire) and disease severity (clinical assessments of body functions and activities) in 40 boys with Duchenne muscular dystrophy (19 ambulant, 21 wheelchair dependent) who were in different phases of the disease and underwent life-limiting events such as the loss of the ability to ambulate and the ability to lift the arms. In addition, we compared boys’ health-related quality of life perceptions with that of their parents. The participants’ health-related quality of life was similar to healthy peers’ and not influenced by disease severity, except for the physical domain. Parents scored much lower than the boys on the KIDSCREEN-52 domains Self Perception, Moods and Emotions, and Bullying. The latter finding needs attention in the management of Duchenne muscular dystrophy.