K. Eger

Camptocormia phenotype of FSHD: a clinical and MRI study on six patients

Recently it has been postulated that there is an atypical facioscapulohumeral muscular dystrophy (FSHD) phenotype with isolated axial myopathy. Involvement of paraspinal and limb muscles was evaluated in six patients with molecularly proven FSHD and a predominant bent spine phenotype. Consistent with the camptocormia phenotype, the most severely affected muscles in all six patients were the thoracic and lumbar spinal tract together with hamstrings. MRI disclosed severe axial muscle degeneration but mostly subclinical involvement of limb muscles. The involvement of hip extensor muscles in FSHD might considerably contribute to the clinical phenotype of camptocormia due to axial muscle involvement.

Beevor’s sign in facioscapulohumeral muscular dystrophy: an old sign with new implications

Beevor’s sign, an upward deflection of the umbilicus on flexion of the neck, is the result of paralysis of the inferior portion of the rectus abdominis muscle, so that the upper fibers predominate, pulling the umbilicus upwards. The condition may be caused by spinal cord injury at or below the level of Th10. It has also been observed in patients with facioscapulohumeral muscular dystrophy (FSHD). Positive Beevor’s sign has been described as a sign of more than 90% sensitivity and specificity with regard to diagnosis of FSHD. We investigated 28 patients with FSHD, proven by genetic analysis, and 65 non-FSHD patients with other neuromuscular diseases. In 13 patients classical FSHD phenotype was observed, in 15 patients phenotype was atypical. Beevor’s sign was positive in 15 out of 28 FSHD patients as well as in two of the 65 non-FSHD patients. In patients with typical FSHD phenotype, Beevor’s sign was positive in 11/13. Only 4/15 patients with atypical FSHD phenotype showed Beevor’s sign. Beevor’s sign is less frequent in patients with atypical phenotype. Although Beevor’s sign is significantly more frequent in FSHD patients than in patients with other neuromuscular diseases, Beevor’s sign is not as sensitive as previously reported. However, especially in atypical cases, Beevor’s sign might help in the diagnosis of FSHD.

MuSK–antibody positive pure ocular myasthenia gravis

Sirs: Antibodies (Ab) against the muscle-specific receptor tyrosine kinase (MuSK) were found in 38–58 % of patients with so-called seronegative, (that means acetylcholine receptor (AChR) Ab negative) generalized myasthenia gravis (MG) [1–3]. Ocular symptoms are frequently the initial findings in MuSK-Ab-positive MG [4]. In two series, however, MuSK-Abs could not be detected in 18 and 13 patients with pure ocular MG, respectively [4, 5]. Therefore, it was concluded that patients with MuSK-Ab carry a high risk of early generalization. We present a case with MuSK-Ab positive MG and isolated bilateral ptosis for three years. The 57-year old German female patient had noticed increasing bilateral ptosis, worse in the evening, which eventually impaired vision. The symptoms had lasted for at least two years. Clinical examination showed bilateral symmetrical ptosis with a palpebral fissure of 5 mm. Ptosis did not improve after i. v. application of edrophonium chloride. There was no evidence of further ocular, bulbar, or generalized involvement. There was no pathological decrease in the orbicularis oris muscle power after repetitive 3/s stimulation of the facial nerve. AChR-, titin-, MAK-, TAK-, and TRAK antibodies were not found. The MuSK-antibody ratio was 13 (normal ratio < 10, Laboratory Prof. Seelig & Kollegen, Karlsruhe, Germany) [6]. Ptosis responded well upon treatment with up to 330 mg/d pyridostigmine and 150 mg/d azathioprine (palpebral fissure became 8–10 mm wide). No generalized symptoms have developed during treatment for twelve months. During that time the MuSK-antibody ratio decreased to a ratio of 8.5. Out of our five patients with MuSK-Ab two others showed initially isolated ocular involvement: One female patient’s symptoms became generalized within three months. The other female patient has been showing isolated ptosis for 15 months (being untreated for two months, treated for 13 months). Initially isolated ocular symptoms occur in about 50 % of AChRAb positive MG. The progression from pure ocular MG into generalized MG is very rare after a disease course of > 2 years. Therefore, most of the studies on ocular MG used an observation period of two years [7–9]. However, neither the Ossermann Classification nor the MGFA Clinical Classification refers to a temporal category to distinguish between MG with initial ocular symptoms and pure ocular MG [10, 11]. Within two years 34–86 % of untreated AChR-Ab positive patients with ocular involvement, but only 7–17 % of patients treated with immunosuppressive drugs progressed into a generalized MG [7–9]. Initial ocular symptoms, either isolated or associated with other symptoms were found in 6/10 patients with MuSK-Ab positive generalized MG [4]. Recently, one MuSK-Ab positive female with ptosis and diplopia was reported, for whom immunosuppressive treatment was started three months after the onset of ocular symptoms and which did not generalize during a course of more than twelve months [12]. Since our patient remained with only ocular symptoms for at least two years without treatment her disorder can clearly be classified as ocular myasthenia. In conclusion our case indicates that a small proportion of cases with MuSK-Ab stay as a pure ocular MG over a period exceeding two years.

A family with PROMM not linked to the recently mapped PROMM locus DM2

Proximal myotonic myopathy is an autosomal dominantly inherited multisystem disorder, clinically similar to but genetically distinct from myotonic dystrophy (DM). A recently mapped second locus for myotonic dystrophy was thought to be an attractive candidate locus for PROMM, and this hypothesis was supported by reports of linkage to this locus in some PROMM families. We present a large German pedigree with PROMM in which linkage to this locus could be excluded, showing that PROMM is genetically heterogeneous.

Proximal myotonic myopathy (PROMM). Clinical variability within a family

ZusammenfassungDie proximale myotone Myopathie (PROMM) ist eine seit 1994 bekannte autosomal- dominant vererbte Erkrankung. Symptome der PROMM sind beinbetonte, vorwiegend proximale Paresen, leichte klinische oder elektromyographische Myotonie und Katarakt. Eine Trinukleotid-(CTG)-Repeatexpansion auf dem Genort der Dystrophia myotonica (DM) läßt sich nicht nachweisen. Im zerebralen Magnetresonanztomogramm zeigen sich bei der Hälfte der Patienten Veränderungen der weißen Substanz. In der vorliegenden Arbeit werden 7 Patienten mit PROMM aus einer Familie vorgestellt. Die Variabilität der Symptome reichte von allein subklinischen myotonen Veränderungen im Elektromyogramm oder alleinigem Auftreten einer Katarakt bis zu schweren proximalen, beinbetonten Paresen mit schmerzhaften Parästhesien. Die PROMM stellt somit einerseits eine wichtige Differentialdiagnose der DM dar und andererseits aufgrund der proximalen Paresen auch von Gliedergürtelsyndromen, metabolischen und endokrinen Myopathien und Myositiden. Neben dem EMG-Befund und dem Ausschluß des Gendefektes der DM kann aufgrund der Variabilität der Symptome die Untersuchung von Verwandten zur Diagnosesicherung notwendig sein.SummaryProximal myotonic myopathy (PROMM) is a newly described autosomal dominant inherited disorder characterized by predominant proximal weakness of the legs, mild clinical myotonia or myotonia on electromyograms (EMG), cataracts and slight elevation of liver enzymes. The trinucleotide (cytosine, thymine, and guanine) repeat size of the myotonic dystrophy (DM) gene is normal. Magnetic resonance imaging of the brain may reveal a peculiar pattern of white matter abnormalities. We describe seven patients in a new family with PROMM. The only symptoms may be subclinical myotonic changes in the EMG or cataracts, but symptoms may also include severe proximal weakness of the legs and painful paraesthesia. PROMM is an important differential diagnosis of myotonic dystrophy; and because of the proximal weakness it is also a differential diagnosis of other muscle diseases such as limb girdle dystrophy, metabolic and endocrine myopathies, and myositis. Because of the variability of the symptoms, for the definite diagnosis of PROMM it may require the examination of other family members.

Polymyositis associated with thymoma

ZusammenfassungNeuromuskuläre Begleiterkrankungen eines Thymoms sind die Myasthenia gravis, die Polymyositis, die Dermatomyositis sowie die Neuromyotonie. Während 50% der Thymompatienten eine Myasthenia gravis entwickeln, ist die Polymyositis mit einer Häufigkeit von weniger als 5% bei Thymomen als paraneoplastische Erkrankung kaum bekannt.Es wird ein Patient mit Thymom, Polymyositis und Myasthenia gravis vorgestellt. Bei gleichzeitigem Bestehen von Myositis und Myasthenia gravis vermischen sich die diagnostischen Kriterien (Serum-CK, EMG, Augenbeteiligung) beider Erkrankungen. Dies kann die Diagnose und damit auch die Therapie beider Erkrankungen erheblich erschweren.SummaryNeuromuscular diseases accompanying thymoma include myasthenia gravis, polymyositis, dermatomyositis, and neuromyotonia. Usually 50% of patients with thymoma develop myasthenia gravis. However, only 5% show polymyositis as an accompanying paraneoplastic phenomenon. We report the case of a patient with thymoma showing myasthenia gravis as well as polymyositis. Due to the simultaneous occurrence of these paraneoplastic diseases, the criteria for exact diagnosis (serum creatine kinase, EMG, ocular involvement) overlap. This diagnostic dilemma can appreciably complicate the therapeutic approach.Neuromuscular diseases accompanying thymoma include myasthenia gravis, polymyositis, dermatomyositis, and neuromyotonia. Usually 50% of patients with thymoma develop myasthenia gravis. However, only 5% show polymyositis as an accompanying paraneoplastic phenomenon. We report the case of a patient with thymoma showing myasthenia gravis as well as polymyositis. Due to the simultaneous occurrence of these paraneoplastic diseases, the criteria for exact diagnosis (serum creatine kinase, EMG, ocular involvement) overlap. This diagnostic dilemma can appreciably complicate the therapeutic approach.

Facioscapulohumeral muscular dystrophy. The spectrum of clinical manifestations and molecular genetic changes

ZusammenfassungObwohl das Gen der fazioskapulohumeralen Muskeldystrophie (FSHD) nicht identifiziert ist, gilt der Nachweis einer 4q35-Deletion als diagnostischer Marker dieser Erkrankung. In der vorliegenden Untersuchung wurden 46 konsekutive symptomatische Patienten mit einer 4q35-FSHD-Deletion oder typischen klinischen Manifestationen einer FSHD evaluiert. Die Patienten wurden in 3 Gruppen unterteilt: Patienten mit aufgrund etablierter Kriterien typischen klinischen Manifestationen einer FSHD und der FSHD-4q35-Deletion (72%),Patienten mit atypischen (Nicht-Landouzy-Dejerine-Phänotyp) klinischen Manifestationen und FSHD-4q35-Deletion (17%) und Patienten mit typischen Symptomen einer FSHD ohne FSHD-4q35-Deletion (11%).Die Vielfalt der klinischen Manifestationen bei den “atypischen” Patienten zeigt, dass bisherige klinische Kriterien der FSHD offensichtlich zu eng gefasst sind. Andererseits erscheint der Phänotyp einer Landouzy-Dejerine-FSHD auch durch andere genetische Defekte als die 4q35-Deletion verursacht werden zu können.SummaryAlthough the gene for facioscapulohumeral muscular dystrophy (FSHD) has not been identified so far, 4q35 deletion represents a diagnostic marker of the disease. In the present study, 46 consecutive symptomatic patients with 4q35 FSHD deletions or typical FSHD clinical features were evaluated.The patients were divided into three groups: 33 patients (72%) with typical FSHD phenotype and 4q35 FSHD deletion, eight (17%) with atypical (non-Landouzy-Dejerine) FSHD phenotype but with 4q35 FSHD deletion, and five patients (11%) with the typical FSHD phenotype but without FSHD 4q35 deletion. Apparently, the 4q35 deletion is associated not only with Landouzy-Dejerine FSHD but also with a variety of “atypical” FSHD forms.On the other hand, the Landouzy-Dejerine FSHD phenotype is possibly a polyetiological syndrome caused in some patients by other genetic effects than 4q35 deletion.

Lactate production upon short-term non–ischemic forearm exercise in mitochondrial disorders and other myopathies

BackgroundThe nonischemic forearm exercise test (NIFET) has been shown to be as effective as the classic ischemic forearm exercise test (IFET) in the diagnosis of patients with Mc Ardle disease. Recently, the lactate increase normalized to the mechanical energy production in NIFET was suggested to have a intermediate sensitivity and satisfactory specifity for the screening of mitochondrial disorders.MethodsNIFET at 80% maximal contraction force (MCF) was performed in normal controls (n = 41), patients with mitochondrial disorders (n = 15) and other myopathies (diseased controls, n = 20). 26 healthy volunteers also underwent IFET at 80% MCF. The ratio of lactate increase and workload was defined as specific lactate production (mmol x s/N x l).ResultsIn normal controls there was no significant different lactate increase during NIFET and IFET. The workload performed showed only a weak significant positive correlation with the lactate increase in the NIFET in normal controls (r2 = 0.20) but not in IFET and NIFET with patients. A moderate negative correlation of specific lactate production and the absolute workload was found in all groups and in both protocols (r2 = 0.22–0.34). The specific lactate production was highest in patients with other myopathies, intermediate in patients with mitochondrial disorders and lowest in normal controls. NIFET showed a sensitivity of only 20 % and a specifity of 95% for normal controls, but only 75 % for diseased controls.ConclusionThe specific lactate production during NIFET is neither sufficently specific nor sensitive for the diagnosis of mitochondrial disorders. Increased specific lactate production during rest–to–work transition period might be caused by increased acetyl group deficits.