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Josef Finsterer Neurology & Neurophysiology Center, Vienna, AustriaCorrespondence: Josef Finsterer, Email fifigs1@yahoo.de

We read with interest the article by Gupta et al about 18 patients with occupational nerve injuries caused by metallic foreign bodies while operating lathes. Two patients were found to have more than one nerve injury and one patient had an associated vascular injury. The most commonly injured nerve was the median nerve. The most common site for nerve injury was the forearm. Combined lesions most commonly affected the ulnar and median nerves. It was concluded that the costs of traumatic peripheral nerve injuries are significant because they occur particularly frequent in young, previously healthy and economically active people. The study is impressive, but some points require further discussion.

Josef Finsterer Neurology & Neurophysiology Center, Vienna, AustriaCorrespondence: Josef Finsterer, Neurological Department, Neurology and Neurophysiology Center, Postfach 20, Vienna, 1180, Austria, Tel/Fax +43-1-5861075, Email fifigs1@yahoo.de

Josef Finsterer Neurology & Neurophysiology Center, Vienna, AustriaCorrespondence: Josef Finsterer, Neurology & Neurophysiology Center, Postfach 20, Vienna, 1180, Austria, Tel/Fax +43-1-5861075, Email fifigs1@yahoo.de

Josef Finsterer,1 Fulvio A Scorza2 1Neurology & Neurophysiology Center, Vienna, Austria; 2Disciplina de Neurociência, Universidade Federal de São Paulo/Escola Paulista de Medicina (UNIFESP/EPM), São Paulo, BrasilCorrespondence: Josef Finsterer, Neurology & Neurophysiology Center, Postfach 20, Vienna, 1180, Austria, Tel/Fax +43-1-5861075, Email fifigs1@yahoo.de View the original paper by Dr Assiri and colleagues

Josef FinstererKrankenanstalt Rudolfstiftung, Messerli Institute, Vienna, AustriaObjectives: Barth syndrome is an ultra-rare, infantile-onset, X-linked recessive mitochondrial disorder, primarily affecting males, due to variants in TAZ encoding for the cardiolipin transacylase tafazzin. This review aimed to summarize and discuss recent and earlier findings concerning the etiology, pathogenesis, clinical presentation, diagnosis, treatment, and outcome of Barth syndrome.Method: A literature review was undertaken through a MEDLINE search.Results: The phenotype of Barth syndrome is highly variable but most frequently patients present with hypertrophic/dilated/non-compaction cardiomyopathy, fibroelastosis, arrhythmias, neutropenia, mitochondrial myopathy, growth retardation, dysmorphism, cognitive impairment, and other, rarer features. Lactic acid and creatine kinase, and blood and urine organic acids, particularly 3-methylglutaconic acid and monolysocardiolipin, are often elevated. Cardiolipin is decreased. Biochemical investigations may show decreased activity of various respiratory chain complexes. The diagnosis is confirmed by documentation of a causative TAZ variant. Treatment is symptomatic and directed toward treating heart failure, arrhythmias, neutropenia, and mitochondrial myopathy.Conclusions: Although Barth syndrome is still an orphan disease, with fewer than 200 cases described so far, there is extensive ongoing research with regard to its pathomechanism and new therapeutic approaches. Although most of these approaches are still experimental, it can be expected that causative strategies will be developed in the near future.Keywords: Barth syndrome, tafazzin, TAZ, cardiomyopathy, non-compaction, X-linked

Myotonic dystrophy type 2 (MD2) is a multisystem disease, predominantly affecting the proximal limb muscles, eyes, endocrine organs, heart and intestines. Longterm asymptomatic creatine kinase (hyper-CKemia) of more than 20 years duration, in association with hyperlipidemia and diabetes, as a manifestation of MD2 has not been reported. A 52-year-old female with a history of hyper-CKemia since the age of 32 years associated with diabetes, hyperlipidemia and hyperuricemia, developed anginal chest pain and proximal muscle weakness together with clinical myotonia when opening the fists at age 51 years. Examination revealed a left anterior hemiblock, sensorimotor neuropathy, extensive myotonic discharges on needle electromyography (EMG) and a CCTG-expansion of 134 bp on the ZNF9 gene. The family history was positive for hyper-CKemia and muscle weakness. In addition, over the previous years, she had developed vesico-ureteral reflux, cutaneous melanoma, renal cysts, cervix dysplasias, thrombocytosis, cataracts, arterial hypertension, heterozygous Factor V Leiden mutation, cholecystolithiasis, multiple ovarial cysts and vitamin D deficiency. Asymptomatic, long-term hyper-CKemia in association with multisystem disease should raise the suspicion of a MD2. Rare manifestations of MD2 may be thrombocytosis, hyperuricemia, vesico-ureteral reflux, gallstones, hypertension and cyst formation. In patients with asymptomatic hyper-CKemia, needle EMG should be considered. Myotonic dystrophy type 2 may take a mild course over many years if the CCTG-expansion is short.

Josef Finsterer,1 Sinda Zarrouk-Mahjoub2 1Municipal Hospital Rudolfstiftung, Vienna, Austria; 2Genomics Platform, Pasteur Institute of Tunis, Tunis, Tunisia Objectives: Mitochondrial disorders (MIDs) frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) at onset or evolve into MIMODS during the course. This study aimed to find which organs and/or tissues are most frequently affected by MIMODS, which are the most frequent abnormalities within an affected organ, whether there are typical MIMODS patterns, and to generate an MIMODS score to assess the diagnostic probability for an MID.Methods: This is a retrospective evaluation of clinical, biochemical, and genetic investigations of adult patients with definite MIDs. A total of 36 definite MID patients, 19 men and 17 women, aged 29–82 years were included in this study. The diagnosis was based on genetic testing (n=21), on biochemical investigations (n=17), or on both (n=2).Results: The number of organs most frequently affected was 4 ranging from 1 to 9. MIMODS was diagnosed in 97% of patients. The organs most frequently affected were the muscle (97%), central nervous system (CNS; 72%), endocrine glands (69%), heart (58%), intestines (55%), and peripheral nerves (50%). The most frequent CNS abnormalities were leukoencephalopathy, prolonged visually evoked potentials, and atrophy. The most frequent endocrine abnormalities included thyroid dysfunction, short stature, and diabetes. The most frequent cardiac abnormalities included arrhythmias, systolic dysfunction, and hypertrophic cardiomyopathy. The most frequent MIMODS patterns were encephalomyopathy, encephalo-myo-endocrinopathy, and encepalo-myo-endocrino-cardiopathy. The mean ± 2SD MIMODS score was 35.97±27.6 (range =11–71). An MIMODS score >10 was regarded as indicative of an MID.Conclusion: Adult MIDs manifest as MIMODS in the vast majority of the cases. The organs most frequently affected in MIMODS are muscles, CNS, endocrine glands, and heart. An MIMODS score >10 suggests an MID. Keywords: multisystem disease, mitochondrial cytopathy, multiorgan, mitochondriopathy, cardiomyopathy, encephalomyopathy

Josef Finsterer,1 Sinda Zarrouk-Mahjoub2 1Krankenanstalt Rudolfstiftung, Vienna, Austria; 2University of Tunis El Manar, Genomics Platform, Pasteur Institute of Tunis, Tunis, Tunisia We have read with interest the article by Garcia et al1 about the effect of visual impairment on psychological well-being with regard to mood, interpersonal interactions, and career-related goals.1 Among the 103 Leber’s hereditary optic neuropathy (LHON) patients, half became depressed with negative impacts on interpersonal relations and career goals. At diagnosis, older age corresponded to higher depression prevalence than young age. We have the following comments and concerns.View the original paper by Garcia and colleagues.

Josef Finsterer,1 Sinda Zarrouk-Mahjoub2 1Krankenanstalt Rudolfstiftung, Vienna, Austria; 2Genomics Platform, Pasteur Institute of Tunis, Tunisia Abstract: Leber’s hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disorder with bilateral loss of central vision primarily due to mitochondrial DNA (mtDNA) mutations in subunits of complex I in the respiratory chain (primary LHON mutations), while other mtDNA mutations can also be causative. Since the first description, it is known that LHON is not restricted to the eyes but is a multisystem disorder additionally involving the central nervous system, ears, endocrinological organs, heart, bone marrow, arteries, kidneys, or the peripheral nervous system. Multisystem involvement may start before or after the onset of visual impairment. Involvement of organs other than the eyes may be subclinical depending on age, ethnicity, and possibly the heteroplasmy rate of the responsible primary LHON mutation. Primary LHON mutations may rarely manifest without ocular compromise but with arterial hypertension, various neurodegenerative diseases, or Leigh syndrome. Patients with LHON need to be closely followed up to detect at which point organs other than the eyes become affected. Multiorgan disease in LHON often responds more favorably to symptomatic treatment than the ocular compromise. Keywords: mitochondrial DNA, heteroplasmy, respiratory chain, LHON, genotype–phenotype correlation

Josef FinstererKrankenanstalt Rudolfstiftung, Messerli Institute, Vienna, AustriaWith interest I read the article by Madhoun et al about a 4.5-year-old female with multisystem mitochondrial disorder (MID) due to the variant c.251T>C in the ATAD3A gene.1 The patient was reported to have profited from the ketogenic diet (KD) by slowing the progression of cerebellar atrophy, and improving vitality, interaction, moaning, carrying, tremor, and weakness. I have the following comments and concerns.View the original paper by Madhoun and colleagues.

Josef Finsterer,1 John Hayman21Krankenanstalt Rudolfstiftng, Vienna, Austria; 2Department of Pathology, University of Melbourne, Victoria, AustraliaBackground: Charles Darwin (CD), “father of modern biology,” suffered from multisystem illness from early adulthood. The most disabling manifestation was cyclic vomiting syndrome (CVS). This study aims at finding the possible cause of CVS in CD.Methods: A literature search using the PubMed database was carried out, and CD's complaints, as reported in his personal writings and those of his relatives, friends, colleagues, biographers, were compared with various manifestations of mitochondrial disorders (MIDs), known to cause CVS, described in the literature.Results: Organ tissues involved in CD's disease were brain, nerves, muscles, vestibular apparatus, heart, gut, and skin. Cerebral manifestations included episodic headache, visual disturbance, episodic memory loss, periodic paralysis, hysterical crying, panic attacks, and episodes of depression. Manifestations of polyneuropathy included numbness, paresthesias, increased sweating, temperature sensitivity, and arterial hypotension. Muscular manifestations included periods of exhaustion, easy fatigability, myalgia, and muscle twitching. Cardiac manifestations included episodes of palpitations and chest pain. Gastrointestinal manifestations were CVS, dental problems, abnormal seasickness, eructation, belching, and flatulence. Dermatological manifestations included painful lips, dermatitis, eczema, and facial edema. Treatments with beneficial effects to his complaints were rest, relaxation, heat, and hydrotherapy.Conclusion: CVS in CD was most likely due to a multisystem, nonsyndromic MID. This diagnosis is based upon the multisystem nature of his disease, the fact that CVS is most frequently the manifestation of a MID, the family history, the variable phenotypic expression between affected family members, the fact that symptoms were triggered by stress, and that only few symptoms could not be explained by a MID.Keywords: hyperemesis, cyclic vomiting, fatigue, metabolic disease, mitochondrial disorder, multisystem disorder, respiratory chain

Josef Finsterer,1 Claudia Stollberger,2 Elisabeth Stubenberger,3 Sasan Tschakoschian4 1Krankenanstalt Rudolfstiftung, Vienna, Austria; 2Medical Department, Krankenanstalt Rudolfstiftung, Vienna, Austria; 3Thoracic Surgery Department, Vienna, Austria; 4Interne Lungenabt, Vienna, Austria Background: This case report documents the affliction of the lymph vessels as a phenotypic feature of neurofibromatosis-1 (NF-1). Methodology: Routine transthoracic echocardiography, computed tomography scan of the thorax, magnetic resonance angiography of the renal arteries, and conventional digital subtraction angiography were applied. Comprehensive NF-1 mutation analysis was carried out by fluorescence in situ hybridization analysis, long-range reverse transcriptase polymerase chain reaction, and multiple-ligation probe assay. All other investigations were performed using routine, well-established techniques. Results: The subject is a 34-year-old, half-Chinese male; NF-1 was suspected at age 15 years for the first time. His medical history included preterm birth, mild facial dysmorphism, "café au lait" spots, subcutaneous and paravertebral fibromas, multifocal tachycardia, atrial fibrillation, and heart failure in early infancy. Noncalcified bone fibromas in the femur and tibia were detected at age 8 years. Surgical right leg lengthening was carried out at age 11 years. Bilateral renal artery stenosis, stenosis and aneurysm of the superior mesenteric artery, and an infrarenal aortic stenosis were detected at age 15 years. Leg edema and ectasia of the basilar artery were diagnosed at age 18 years. After an episode with an erysipela at age 34 years, he developed pericardial and pleural effusion during a 4-month period. Stenosis of the left subclavian vein at the level of thoracic duct insertion was detected. After repeated pleural punctures, pleural effusion was interpreted as chylothorax. Reduction of lymph fluid production by diet and injection of talcum into the pleural cavity had a long-term beneficial effect on the chylothorax. Leg edema and chylothorax were attributed to affliction of the lymph vessels by the NF-1. Discussion: Lymphangiopathy resulting in impaired lymph fluid flow and sequestration of lymph fluid into the pleural sinus and the legs may be a rare phenotypic feature of NF-1. Keywords: angiodysplasia, lymph edema, lymph fluid, Recklinghausen's disease, genetics, mutation

Adam Bastovansky,1 Kathrin Ziegler,2 Claudia Stöllberger,2 Josef Finsterer31Department of Radiology, 2Medical Department, Krankenanstalt Rudolfstiftung, Vienna, Austria; 3Danube University Krems, Krems, AustriaBackground: Peripheral embolism to the lower extremities may mimic disc prolapse with severe consequences.Case report: A 71-year-old male with a history of chronic alcoholism developed low back pain radiating to both lower extremities in a nonradicular distribution and bilateral dysesthesias of the distal lower legs after lifting a heavy weight. Given that magnetic resonance imaging (MRI) of the lumbar spine showed disc herniation in L3/4 and L4/5, he was scheduled for laminectomy but was unable to undergo surgery due to thrombocytopenia. After transfer to another hospital, persistence of symptoms and signs, absent pulses on the distal lower legs, and rhabdomyolysis with temporary renal insufficiency, peripheral embolism with compartment syndrome was suspected. Magnetic resonance angiography revealed occlusion of the right superficial femoral artery and long high-grade stenosis of the left superficial and profound femoral arteries and distal arteries. He successfully underwent embolectomy and fasciotomy.Conclusions: If lumbar pain is not radicular, peripheral pulses are minimally palpable, and distal limbs are cold and show livid decolorization, peripheral embolism is much more likely than disc herniation, particularly if the patient's history is positive for atrial fibrillation. MRI of the lumbar spine must be interpreted in conjunction with clinical presentation.Keywords: embolism, compartment syndrome, neurosurgery, embolectomy, fasciotomy, rhabdomyolysis

Josef Finsterer,1 Sinda Zarrouk-Mahjoub21Krankenanstalt Rudolfstiftung, Vienna, Austria; 2Genomics Platform, Pasteur Institute of Tunis, Tunis, Tunisia We read with great interest the article, by Kono et al, about a 32-year-old male with Duchenne muscular dystrophy (DMD), who was admitted for dilated cardiomyopathy manifesting as heart failure, left bundle branch block, Mobitz-II block, bradycardia, and arterial hypotension. He profited from implantation of a cardiac resynchronization therapy-D system with a defibrillator and beta-blocker treatment. View original article by Kono et al.