Myoclonus-dystonia: clinical and genetic evaluation of a large cohort.

BACKGROUND: Myoclonus-dystonia (M-D) is an autosomal dominant inherited movement disorder. Various mutations within the epsilon-sarcoglycan (SGCE) gene have been associated with M-D, but mutations are detected in only about 30% of patients. The lack of stringent clinical inclusion criteria and limitations of mutation screens by direct sequencing might explain this observation. METHODS: Eighty-six M-D index patients from the Dutch national referral centre for M-D underwent neurological examination and were classified according to previously published criteria into definite, probable and possible M-D. Sequence analysis of the SGCE gene and screening for copy number variations were performed. In addition, screening was carried out for the 3 bp deletion in exon 5 of the DYT1 gene. RESULTS: Based on clinical examination, 24 definite, 23 probable and 39 possible M-D patients were detected. Thirteen of the 86 M-D index patients carried a SGCE mutation: seven nonsense mutations, two splice site mutations, three missense mutations (two within one patient) and one multiexonic deletion. In the definite M-D group, 50% carried an SGCE mutation and one single patient in the probable group (4%). One possible M-D patient showed a 4 bp deletion in the DYT1 gene (c.934_937delAGAG). CONCLUSIONS: Mutation carriers were mainly identified in the definite M-D group. However, in half of definite M-D cases, no mutation could be identified. Copy-number variations did not play a major role in the large cohort.

Probably anti-Tr associated paraneoplastic cerebellar degeneration as initial presentation of a squamous cell carcinoma of the lung.

Paraneoplastic cerebellar degeneration (PCD) is the most frequent paraneoplastic syndrome affecting the brain. Until now, anti-Tr associated PCD was only seen in patients with Hodgkin's disease. We report a male patient who presented with a progressive ataxia, affecting predominantly the lower limbs and a cerebellar dysarthria. Extensive diagnostic approach initially showed no evidence of tumor. The patient was found to have anti-Tr antibodies in his serum. Fourteen months after onset of symptoms a whole body PET-scan showed a pathological focus at the right hilus of the lungs. A mediastinoscopy was performed and peribronchial node sampling was done. The anatomopathological analysis revealed a non-well differentiated squamous cell carcinoma. This is the first report about the association between an anti-Tr associated PCD and squamous cell carcinoma.

Central nervous system metastases of pulmonary adenocarcinoma mimicking neurofibromatosis type 2.

We report a case of a 51-year-old man presenting with rapidly progressive unilateral tinnitus, hearing loss and imbalance. Neuroimaging revealed bilateral VIIIth cranial nerve masses and multiple cerebral and spinal cord lesions that were interpreted as being acoustic schwannomas and multiple meningeomas. An initial tentative diagnosis of neurofibromatosis type 2 (NF2) was made. Both clinical and radiological evolution were atypical for NF2 and the initial diagnosis of NF2 was questioned. Additional technical investigations demonstrated a pulmonary adenocarcinoma. Postmortem examination confirmed that this patient had multiple central nervous system metastases of a primary pulmonary adenocarcinoma, presenting clinically and neuroradiologically as a probable neurofibromatosis type 2. Clinicians should be aware of the rare possibility of central nervous system metastases mimicking NF2.

Wegener's granulomatosis presenting as otomastoiditis. A case report.

A 55-year-old male presented with left-sided otorrhoea, hearing loss and tinnitus of 3 months duration. On clinical examination polypoid tissue was seen prolapsing in the external ear canal. A CT scan of the mastoid cells and middle ear showed otomastoiditis with osteolysis. Oral antibiotic therapy and eardrops were started. When a facial nerve paresis appeared one month later, a mastoidectomy was performed. The mastoid cells and middle ear were filled with a connective tissue-like substance. Postoperative corticosteroids were administered. Despite the therapy the facial nerve problem aggravated and the patient developed severe parietotemporal headache, meningeal irritation and somnolence. The diagnosis of neurosarcoidosis was hypothesised. Blood analysis, including c-ANCA's, culture of the otorrhoea and biopsies of the connective tissue were inconclusive. A CT scan of the brain showed thickening of the left tentorium. A biopsy of the dura indicated a diagnosis of Wegener's granulomatosis. The patient was treated with immunosuppressive medication with satisfactory results.

Increased GFAp levels in CSF as a marker of organicity in patients with Alzheimer's disease and other types of irreversible chronic organic brain syndrome.

Glial fibrillary acidic protein (GFAp), an astrocyte-specific protein, was determined in cerebrospinal fluid (CSF) of adults and children with global cognitive dysfunction. In children CSF-GFAp values were not closely associated with organic brain disease. However, GFAp values in CSF were increased in 65 of 121 samples of adults with dementia, independent of its cause. GFAp values were not correlated with the severity of the dementia. Increased levels in the CSF are believed to indicate reactive gliosis in most patients with dementia, whereas GFAp levels in encephalitic patients normalize after clinical recovery.

Dementia paralytica in a fifteen-year-old boy.

A 15-year-old boy, whose history revealed an unremarkable pregnancy, birth and neonatal period and who had shown a normal motor and mental development, presented at the hospital with deterioration of cognitive functions since the age of 7. He was bedridden with manifest ataxia involving all limbs, anisocoria and a sluggish to absent pupil reaction to light. Syphilis serology was positive with a Venereal Disease Research Laboratory (VDRL) titer of 1:256 and a Treponema pallidum Haemagglutination Assay (TPHA) titer of 1:163840. Cerebrospinal fluid (CSF) protein concentration was 55 mg/dl and CSF-leucocyte count was 14/mm3 (85% mononuclear cells). CSF-VDRL-titer was 1:16. A diagnosis of congenitally acquired dementia paralytica was made, since the boy's parents' clinical exam and serology results were suggestive for latent syphilis. Although cognition was still very much deteriorated five months following penicillin treatment, clinical examination revealed partial recuperation. Screening for syphilis should be part of routine testing in every subject presenting with cognitive deterioration, regardless of age.

Perfusion and thallium single photon emission computed tomography in herpes simplex encephalitis.

This is the first report on 201thallium-single photon emission computed tomography (201Tl-SPECT) brain scan of a patient with herpes simplex encephalitis (HSE). The presented 201Tl-SPECT observations are correlated with 99mtechnetium hexamethylpropylene amine oxime (99mTc-HMPAO) perfusion SPECT and magnetic resonance imaging (MRI) findings. Brain 99mTc-HMPAO perfusion SPECT reveals a hyperperfusion in the right temporal lobe with extension to the parietal lobe and a hypoperfusion in the ipsilateral occipital lobe. 201Tl-SPECT shows a fixation in the right temporal lobe coinciding with the gadolinium enhancement on MRI. The right occipital lesion shown by gadolinium captation on MRI and hypoperfusion on 99mTc-HMPAO perfusion SPECT was not evident on the 201Tl SPECT. These findings could illustrate that the lesions might be different pathophysiologically.

Determination in human cerebrospinal fluid of glial fibrillary acidic protein, S-100 and myelin basic protein as indices of non-specific or specific central nervous tissue pathology.

The nervous system specific proteins glial fibrillary acidic protein (GFAp), S-100 and myelin basic protein (MBP) were determined in 535 human cerebrospinal fluid (CSF) samples. The level of all three proteins was increased in CSF of patients with nonselective destructive central nervous tissue disease such as encephalitis, cerebrovascular disease or tumoural compression. The increases in GFAp were more constant, making it a better marker of CNS pathology. Increases in MBP in CSF of patients with acute demyelinating disease were confirmed. S-100 did not seem to give more information as GFAp. Isolated increases of GFAp could be demonstrated in patients with dementia (Alzheimer type or multi-infarct dementia) or syringomyelia. Since CNS of these patients is very rich in fibrillary astrocytes, containing large amounts of GFAp, it is suggested that GFAp is to be considered as a specific marker of fibrillary gliosis in CSF and can be used as a diagnostic tool in dementia and syringomyelia.

Extensive cervical intradural and intramedullary lipoma and spina bifida occulta of C1: a case report.

A 17-year-old boy presented with a 1-year history of progressive gait difficulties and slowing of fine hand movements. On neurological examination there was tetraspasticity, bilateral pes equinovarus and a decreased position sense in the feet. CT and MRI scan of the cervical spine demonstrated a spina bifida occulta of C1, an extensive intradural lipoma from the foramen magnum to C4 with a small intramedullary portion at C3, and a distal syringomyelia reaching down to D12. After excision of the extramedullary portion of the lipoma, there was a marked improvement of the gait and a reduction of the spasticity.

Parkinsonian syndrome after cardiac arrest: radiological and neurochemical changes.

Following a cardiac arrest, a 21-year-old man developed a Parkinson syndrome. This was due to, as shown by brain computerized tomography (CT) and magnetic resonance imaging (MRI), symmetrical infarctions of the basal ganglia, especially the globi pallidi. The levels of homovanillic acid (HVA) in the CSF were lower than normal, pointing to a possible alteration of the central dopaminergic activity. An alteration of the opioid system may also be supposed because of the extremely high levels of methionine-enkephalin (Met-Enk).

Autoantibodies to brain specific proteins in human serum from normal and several pathological conditions.

Autoantibodies to three nervous tissue specific proteins [alpha Albumin (GFA, Eng et al., 1971), S100 (Moore et al., 1968) and MBP (Eylar et al., 1969)] were determined in sera from 270 neurological patients. Control values were established in sera from 21 blood donors. Differences between the control group and several pathological conditions were found, positive results were obtained in sera of patients affected with MS, polyneuropathy and astroglial tumors.

Chronic colchicine-induced myopathy and neuropathy.

The presented case concerns a 77-year old man who had been chronically taking colchicine for treatment of gout. He was admitted because of a transient ischemic cerebrovascular attack with motor aphasia and complained of preexisting paraesthesias in the lower extremities. Neurological examination revealed a global muscular weakness, absent myotatic reflexes and a diminished sensation. Serum creatine kinase (CK) levels were increased and electromyography showed spontaneous fibrillations in deltoid muscles, positive spikewaves in deltoids and anterior tibial muscles. Motor and sensory conduction velocities were mildly reduced. Nerve biopsy findings were compatible with a chronic axonal neuropathy having produced a significant loss of myelinated axons and also denervation features of unmyelinated axons. In muscle, combined neurogenic and myogenic features were found. The former result from the axonal neuropathy. The latter were mainly characterized by focal myofibrillar disorganisation and accumulation of autophagic vacuoles in muscle fibres. The presented neuromuscular symptoms and signs, the increased CK values, the electromyographic and nerve conduction velocity findings as well as nerve and muscle biopsy observations, are consistent with the diagnosis of colchicine-induced myopathy and neuropathy. Furthermore, the disappearance of paraesthesias, normalisation of CK values, and disappearance of fibrillations and positive spike waves in deltoid and anterior tibial muscles on electromyography, after stopping of the colchicine therapy, supported the diagnosis.

Methanol intoxication. Parkinsonism and decreased Met-enkephalin levels due to putaminal necrosis.

Due to methanol intoxication, a 38-year-old male developed permanent parkinsonism with visual impairment. Brain computerized tomography (CT) and magnetic resonance imaging (MRI) revealed cystic resorption of the putamen. An alteration of the central noradrenergic activity and the opioid system can be assumed because of increased dopamine beta-hydroxylase (D beta H) activity and decreased methionine-enkephalin (Met-Enk) levels in the cerebrospinal fluid (CSF).

Clinical and pathophysiological aspects of neurological complications in renal failure.

A review of the neurological complications presenting in uremia and an account of their presumed pathophysiology is given. With the introduction of different dialytic procedures during the last twenty years, the incidence and severity of neurological complications have declined. Nevertheless, some disturbances related to the uremic syndrome fail to respond to dialytic therapy and these therapeutic measures may even be responsible for the appearance of some new abnormalities. The clinical manifestations of uremic encephalopathy and polyneuropathy are presented. The review of the presumed pathophysiology of these syndromes illustrates the still existing controversies. Nevertheless, some promising new lines of research are reviewed. In addition, some complications of uremic treatment, including dialysis disequilibrium syndrome and dialysis encephalopathy are presented.

Transient ischemic attacks associated with amfepramone therapy: a case report.

A 33-year-old man was prescribed amfepramone 75 mg o.i.d. for the treatment of obesity. One week after onset of therapy, he suddenly became agitated and aphasic for several h. A CT scan of the brain was normal. Amfepramone was discontinued. Three days later, there was a second period of agitation and aphasia with a discrete right hemiparesis lasting 12 h. A repeat CT scan and a MRI of the brain were normal. On EEG and brain mapping, alpha-activity was absent over the left hemisphere and a left fronto-temporal delta-focus was found. A Tc-99m HMPAO brain SPECT showed a severe hypoperfusion of the left hemisphere. The next day, the neurological examination was completely normal. Two weeks later, EEG and SPECT had completely normalized. Transient ischemic attacks due to vasospasm were considered to be the most probable clinical diagnosis.

Repeat thallium-201 SPECT in cerebral lymphoma.

The authors report on the contribution of Thallium-201 brain SPECT in the diagnosis and follow-up of a non-immunosuppressed patient, presenting with primary cerebral lymphoma. The tumoral process was at first not diagnosed on CT-scan, but Thallium-201 SPECT suggested a tumoral invasion. During corticosteroid treatment the tumor volume on CT-scan decreased, while on Thallium-201 SPECT there was an enhancement of the accumulation and an increasing tumor to non-tumor ratio. These scintigraphical findings more closely reflected the clinical course and the postmortem results.

Temporal lobe abscess as a complication of cholesteatoma: sequential radiological findings.

Temporal lobe abscess is a rare but known complication of petrosal bone cholesteatoma. We present a case with clinical history, diagnostic imaging and sequential radiological findings of the abscess from the early temporal cerebritis phase till the late full encapsulated abscess. We also succeeded in visualizing the fistula through the tegmen tympani on MR-images.

Long-term intramuscular recombinant DNA interferon alpha 2 therapy in subacute sclerosing panencephalitis: reduction of serum measles antibodies without clinical improvement.

Two patients with subacute sclerosing panencephalitis (SSPE) were treated intramuscularly with recombinant DNA interferon-alpha 2 for 3 and 6 months, respectively. Side effects were minimal. No objective clinical response could be noted. In a patient with stable SSPE, a significant decrease in serum antimeasles antibody levels was observed. This decrease was less pronounced in another patient with evolutive SSPE. The results of this study were compared to findings published previously. The reasons for the lack of clinical efficacy of interferon in SSPE are discussed.