Gene/Protein Disease Symptom Drug Enzyme Compound
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The majority, if not all, of the cases of spontaneous intracranial hypotension result from spontaneous cerebrospinal fluid (CSF) leaks. The disorder has a broad clinical and imaging spectrum with substantial variability in clinical and imaging features, in CSF findings, and in response to treatment. Headache is the most common symptom and is typically orthostatic, but with chronicity the orthostatic features may blur into a chronic, lingering headache. Other clinical features include neck pain, nausea, emesis, interscapular pain, diplopia, dizziness, change in hearing, visual blurring, radicular upper extremity symptoms, and a variety of other, but much less common, manifestations. The most common imaging feature is diffuse pachymeningeal gadolinium enhancement. Other manifestations include imaging evidence of sinking of the brain, subdural fluid collections, enlargement of the pituitary, engorgement of venous sinuses, and engorgement of epidural venous plexus. CSF opening pressure is typically low and CSF analysis may be normal or show increased protein concentration and a primarily lymphocytic pleocytosis. No longer can the entity be simply equated with post-spinal puncture headaches. The pathogenetic core and the independent variable is decrease in CSF volume, whereas clinical imaging and CSF findings, including CSF opening pressures, are all variables dependent on the loss of CSF volume. Many patients respond well to treatment, but some present stubborn therapeutic challenges. A subgroup of patients with orthostatic headaches is gradually recognized who have disorders other than CSF leaks.
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PMID:Spontaneous low cerebrospinal pressure/volume headaches. 1498 83

Spontaneous intracranial hypotension (SIH) is a rare disease which is associated with variety of symptoms and signs including cranial neuropathies. Though diplopia occurred reportedly in about one fourth of SIH cases, trochlear nerve palsy has been reported only one case in the literature. A 71-year-old previously healthy male developed postural headache and nausea. After 15 days, he began to have diplopia caused by right trochlear nerve palsy. He consulted our hospital 2 months later because only diplopia was not recovered. Magnetic resonance imaging (MRI) showed bilateral thin chronic subdural hematoma (CSDH), brain sagging and downward brain stem displacement, but not ischemic change in brain stem. We suspected SIH for right trochlear nerve palsy, and he had symptomatic therapy. Two months later, he had burr hole surgery because of disturbance of consciousness and right hemiparesis due to progressive bilateral-CSDH. To say nothing of disturbance of consciousness and right hemiparesis, his trochlear nerve palsy was completely recovered after surgery at once. Follow-up MRI showed brain sagging and downward brain stem displacement were recovered.
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PMID:[Spontaneous intracranial hypotension associated with trochlear nerve palsy and bilateral chronic subdural hematoma]. 1509 63

Described by Schaltenbrand (1940), spontaneous intracranial hypotension is an unusual syndrome, sometimes revealed by an abducens nerve palsy motivating the patient to consult emergency ophthalmology services. The Authors report the case of a 50-Year-old Turkish woman who presented with diplopia due to a left abducens nerve palsy. These symptoms were associated with headache and nausea. Brain magnetic resonance imaging demonstrated diffuse pachymeningeal enhancement with gadolinium. A lumbar puncture showed low spinal fluid pressure (6 cm H2O), leading to the diagnosis of palsy by spontaneous intracranial hypotension. First, a classic treatment was prescribed with no result: increased water intake, corticoid therapy, and rest. Then a blood patch consisting of an injection of autologous blood by lumbar puncture between the third and fourth lumbar vertebrae to plug the spontaneous leak of spinal fluid, with success. A review of the literature provides information on the physiopathological mechanism, the clinical and imaging symptoms, and the treatment.
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PMID:[Abducens nerve palsy in spontaneous intracranial hypotension]. 1517 48

Spontaneous intracranial hypotension (SIH) is known to cause postural headache, often combined with auditory, and vestibular symptoms, nausea, vomiting, and diplopia. We report a 63-year-old male patient who for the first time developed a depressive episode followed by acute manic symptoms during the course of SIH, both relieved after treatment of the underlying organic disturbance.
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PMID:Organic bipolar disorder occurring together with spontaneous intracranial hypotension. 1531 24

We report clinical findings, risk factors and neurological and cognitive long-term outcome in three Italian children aged 7, 8 and 5, respectively, who experienced cerebral venous sinus thrombosis (CVST). All children presented with headache, associated to nausea, vomiting and papilloedema. None suffered from epileptic seizures. In two of them a paresis of the sixth cranial nerve with diplopia was found. Diagnosis was confirmed by magnetic resonance imaging angiography (angio MRI) in all cases. In all patients plasma levels of protein C, protein S, antithrombin III (AT III), antiphospholipid antibodies (ApA) and homocysteine were detected. Furthermore, factor V Leiden mutation, prothrombin mutation G20210A and MTHFR mutation were searched for. A Protein C reduction was detected in all patients at onset; this finding, however, was not confirmed at follow-up in all of them. At one-year follow-up, neurological examination was normal in all children and neuropsychological assessment, aimed at excluding linguistic and non-linguistic cognitive deficits, revealed normal performances in two of them. In the third child, cognitive assessment confirmed a previously diagnosed developmental dyslexia.
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PMID:Cerebral venous sinus thrombosis in childhood: clinical aspects and neurological and cognitive long-term outcome in three cases. 1562 88

Cerebral hemodynamic and metabolic changes in intracranial hypertension associated with sinus thrombosis have not been well documented. We report pre- and post-treatment changes in cerebral hemodynamic and metabolic parameters in a 50-year-old male who presented intracranial hypertension due to sinus thrombosis, using single-photon emission computed tomography (SPECT) and positron emission tomography (PET). He complained of headache, nausea and double vision and was admitted to our hospital. Neurological examinations on admission revealed papilledema on both sides. Cerebrospinal fluid pressure was 28 mmHg. Cerebral angiography showed occlusion of the superior sagittal sinus and retrograde filling of the ascending cortical veins in the bilateral frontal lobes. 123I-IMP SPECT and 15O-gas PET showed a reduction of cerebral blood flow and oxygen metabolism and an extreme elevation of cerebral blood volume in the bilateral cerebral hemispheres. His complaints resolved after lumbo-peritoneal shunt. Postoperative SPECT/PET studies demonstrated improvement of hemodynamic and metabolic parameters. Intracranial hypertension and associated venous congestion were most likely related to hemodynamic and metabolic abnormalities.
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PMID:[Improvement of cerebral hemodynamic and metabolic parameters in a patient who presented intracranial hypertension due to superior sinus thrombosis after lumbo-peritoneal shunt: case report]. 1577 19

Pachymeningitis is a very rare neurologic manifestation of polyarteritis nodosa (PAN). This report describes a case of acute pachymeningitis that was, initially, misdiagnosed as subdural hematoma on the brain CT of a patient with PAN. A 45-year-old man, who had been diagnosed as having PAN 6 months previously, came back to the emergency room with complaints of sudden headache, nausea, vomiting, and diplopia for 3 days before his hospital admission. Initially, the noncontrast enhanced brain CT findings showed high densities in the bilateral tentorial and posterior parafalcial area, which suggested a small amount of subdural hematoma. However, the subsequent MRI findings revealed pachymeningitis of the bilateral tentoria and falx. He was treated with high-dose steroid and cyclophosphamide pulse therapy. Thereafter, his symptoms gradually resolved.
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PMID:Acute pachymeningitis mimicking subdural hematoma in a patient with polyarteritis nodosa. 1599 74

Lamotrigine is a broadly effective antiepileptic drug in mono- and add-on therapy for children and adolescents with focal and generalized epilepsies. Some epileptologists consider lamotrigine as the drug of primary choice in older school children and adolescents because of its good tolerability (no increase of body weight, no impairment of cognitive functions, due to new data probably no teratogenic properties). Lamotrigine can be used with good efficacy in numerable epilepsy diseases, such as tuberous sclerosis, juvenile neuronal lipofuscinosis and Rett syndrome. The first studies show that lamotrigine is also effective in children under 2 years of age. For therapy of difficult-to-treat epilepsies the combination of lamotrigine with valproate has proved as especially useful. This clinical observation is supported by new results of animal experiments. The dose-dependant and typical CNS side effects vertigo, ataxia, nausea, tremor and diplopia are found most frequently. The rate of allergic skin rashes which was very high before 1998 has decreased markedly by new dosage guidelines and is now as low as in older antiepileptic drugs. Lamotrigine does not impair cognitive functions, especially not memory and language. It has mood-stabilizing features and may improve quality of life. In animal experiments lamotrigine shows antiepileptogenic and neuroprotective effects.
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PMID:[Optimizing epilepsy therapy in children and adolescents with lamotrigine]. 1603 48

The aim of this study was to describe skew deviation and vertical nystagmus as the initial signs for basilar artery thrombosis, a life-threatening disease. A 51-year-old woman complained of vertical diplopia for more than 20 h. A computed tomography of the brain was normal, but subsequently the patient developed additional symptoms including nausea, ventilation problems (dyspnoea) and somnolence. Neuro-ophthalmological evaluation revealed a skew deviation and a vertical nystagmus. Magnetic resonance imaging allowed the diagnosis of basilar artery occlusion. An emergency intervention with cerebral catheter angiography and local intra-arterial thrombolysis was performed. Total recanalization of the basilar artery was achieved resulting in a complete neurological recovery, including the skew deviation and nystagmus. This rare case of skew deviation associated with basilar artery occlusion was a diagnostic challenge and highlights adequate differential diagnosis. Skew deviation is an important clinical sign. In this patient it was the key to a correct diagnosis enabling an immediate and successful intervention.
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PMID:Skew deviation: a precursor to basilar artery thrombosis. 1618 Dec 87

The prognosis for patients with diffuse pontine gliomas (DPG) remains poor. New aggressive innovative treatments are necessary to treat this disease. From 1984 to 1998, eight patients (4M/4F), median age 11 years, with DPG were treated with monthly osmotic blood-brain barrier disruption (BBBD) chemotherapy using intraarterial carboplatin or methotrexate and intravenous cytoxan and etoposide. Patients presented for a median duration of 6 weeks with increased intracranial pressure, long tract signs, diplopia, ataxia, and nausea/vomiting. DPG was demonstrated on magnetic resonance (MR) imaging in seven patients and on CT in one. Two patients had biopsies that showed an astrocytoma and an anaplastic astrocytoma. Three tumors enhanced on MR imaging after contrast administration. Three patients had radiation therapy before BBBD chemotherapy and four afterwards. Two patients had chemotherapy (tamoxifen, topotecan) before BBBD chemotherapy and two afterwards. In general, patients were evaluated with MR imaging every 3 months to monitor for a response to treatment. The median number of chemotherapy cycles that were administered by BBBD was 10, mean 10. Three patients also received one, two, or three cycles of intraarterial chemotherapy without BBBD. One patient that was started on carboplatin was converted to methotrexate, and five that were started on the methotrexate protocol were later converted over to carboplatin. One patient received monthly methotrexate followed by 14 days of procarbazine and one patient started on methotrexate was switched to navelbine. MR imaging demonstrated two partial responses, five patients with stable disease, and one with disease progression. The median time to tumor progression was 15 months with the range from <1 to 40 months. The median survival from the time of diagnosis was 27 months, ranging from 7 to 80 months. The median survival time from the first BBBD or intraarterial treatment was 16.5 months, ranging from 5 to 69 months. One patient was lost to follow-up with an unknown date of death. Although the sample size is small, the TTP and survival times are longer than those previously reported in other DPG series. In addition, the ability to demonstrate stable disease or partial responses in DPG on MR imaging argues for the therapeutic benefit of BBBD chemotherapy. The enhanced delivery of chemotherapy afforded by osmotic BBBD supports the further examination of this treatment modality for patients with DPG.
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PMID:Osmotic blood-brain barrier disruption chemotherapy for diffuse pontine gliomas. 1631 49


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