A patient with Crow-Fukase syndrome associated with pulmonary plasmacytoma]

We here reported a 54-year-old female patient with Crow-Fukase syndrome associated with pulmonary plasmacytoma. She was found to have scattered tumor in 1990. Although the tumor had slowly grown for the last 10 years, she showed no clinical symptoms. Numbness and weakness of lower extremities began in June 1999, and she was referred to Kyoto University Hospital on Oct. 21 1999 for evaluation of progressive symptoms. She had skin pigmentation, edema of the lower extremities, lymphadenopathy, muscle weakness and sensory disturbance in a glove-and-stocking distribution. Serological examination showed monoclonal IgG-lambda gammopathy. Serum vascular endothelial growth factor (VEGF) was markedly elevated. Microscopic studies on biopsied sural nerve demonstrated mild decrease of myelinated fibers. Immunohistochemically, the pulmonary tumor was defined as an IgG (lambda type) plasmacytoma. After treatment with melphalan-prednisolone therapy, the neurological symptoms improved along with decrease of serum VEGF levels as well as the size of pulmonary plasmacytoma. This is the first report of a patient with Crow-Fukase syndrome associated with pulmonary plasmacytoma. This case suggests that growth of pulmonary plasmacytoma might have played an important role in the overproduction of VEGF and thus development of Crow-Fukase syndrome.     

Crow-Fukase syndrome associated with Castleman disease showing hypertrophic cranial pachymeningitis and bilateral internal carotid artery occlusion]

A 51-year-old woman was diagnosed as Crow-Fukase syndrome on July 1997, presenting with lymph node swelling, polyneuropathy, hepatomegaly, hypothyroidism, renal dysfunction, edema and skin change. Lymph node swelling and polyneuropathy improved in some degree after chemotherapy. She was admitted to our hospital on march 6, 1998 because of consciousness disturbance, right hemiparesis and non-fluent aphasia after fever and hypotension. The next day of admission, consciousness disturbance, right hemiparesis and non-fluent aphasia disappeared. MR images of the brain revealed low intensity on a T1-weighted image and high intensity on a T2-weighted image in the left parietal lobe. Furthermore, MR images also revealed diffuse hypertrophic dura matter with enhancement by Gd-DTPA, which made the diagnosis of chronic cranial pachymeningitis. The cerebral angiographies showed bilateral internal carotid artery occlusion. The cerebrospinal fluid showed normal cell count, total protein level of 82 mg/dl, and IgG level of 18 mg/dl. Since there has been very few case reports describing intimate relationship between Crow-Fukase syndrome and pachymeningitis, and between carotid occlusion and pachymeningitis, we speculated that the pachymeningitis might be associated with Crow-Fukase syndrome. Furthermore, pachymeningitis might be a cause of her bilateral carotid occlusion. The number of cases of Crow-Fukase syndrome associated with cerebrovascular disease was very rare. This is the first case which had bilateral internal carotid artery occlusion probably caused by chronic cranial pachymeningitis. Therefore, it is necessary to pay attention to cerebrovascular disease when the patient of Crow-Fukase syndrome is associated with pachymeningitis.     

A case of Crow-Fukase syndrome associated with idiopathic thrombocytopenic purpura

A 40-year-old man was admitted to our hospital because of paresthesia and weakness of the limbs. At the age of 38, he was diagnosed as having an idiopathic thrombocytopenic purpura (ITP) which have been refractory to oral administration of prednisolone and splenectomy. Platelet-associated IgG was elevated markedly at that time. It was, however, only mildly elevated on this admission. He showed polyneuritis, generalized pigmentation, hirsutism, and marked edema on the legs. The bone X-ray disclosed a lytic lesion in the left iliac bone, which was confirmed as a plasmacytoma by bone biopsy. Axonal degeneration with marked loss of myelinated figure was seen on sural nerve biopsy. Serum immunoelectrophoresis revealed his monoclonal IgG was lambda type. Then, he was diagnosed as having a Crow-Fukase syndrome associated with ITP. Plasma exchange, pulse therapy, and irradiation to plasmacytoma resulted in a slight improvement of the polyneuritis and the skin symptoms, and a disappearance of edema. However, ITP has not responded to these therapies. Although the same autoimmune mechanism is suggested in these conditions, we could not clarify how this monoclonal IgG produce both polyneuritis and ITP.     

A case of Crow-Fukase syndrome with increased serum interleukin-6]

We experienced a 47-year-old Japanese female with polyneuropathy, edema, hypertrichosis, hyperpigmentation, and white nail, which were diagnostic as having Crow-Fukase syndrome. Laboratory and radiological evaluation showed neither plasma cell dyscrasia nor monoclonal gammopathy. Increased factor VIII activity and thrombocytosis, which suggested thrombotic tendency, were observed at the exacerbation of clinical symptoms. In her third exacerbation, she presented marked cyanosis in her right foot, and angiography confirmed narrowing of arteries at the ankle. Increased serum interleukin-6 was also observed, and the production of interleukin-6 by endothelial cells of cutaneous angioma was shown. Possible role of interleukin-6 in Crow-Fukase syndrome was discussed.     

Vascular endothelial growth factor and Crow-Fukase syndrome]

Serum vascular endothelial growth factor (VEGF) is highly elevated in patients with Crow-Fukase syndrome (CFS) and is well correlated with the clinical manifestations of CFS. In circulating blood, VEGF is specifically stored in platelets and released during platelet aggregation. To clarify the role of VEGF in the pathomechanism of CFS, we transplanted VEGF secretion tumors in nude mice and studied the pathological findings in these mice. Prominent edema with elevated serum VEGF were found. Organomegaly was also found in liver, spleen and kidney. Pathological findings in these organs were similar to those found in autopsies of CFS patients. In peripheral nerve, mild intraneural edema was seen, however, neuropathy was not prominent. These findings suggest that elevated VEGF may be closely correlated with generalized edema (anasarca). However, it is also important to consider factors such as cytokines and other T cell functions that, in association with VEGF, may be the cause of neuropathy in CFS.     

Steinert disease associated with Klinefelter's syndrome]

Hypogonadism is common in Steinert disease but may also suggest other diagnoses. We report the case of a patient with Steinert's disease who also had Klinefelter syndrome disclosed at 62 years of age by an osteoporotic fracture. Both clinical diagnoses were confirmed by karyotype and genetic analysis. The hypogonadism assigned to the Klinefelter syndrome for this patient may have influenced the clinical expression of the muscular pathology.     

A case of Crow-Fukase syndrome with respiratory failure due to bilateral diaphragmatic paralysis]

A 62-year-old man with well-controlled diabetes mellitus developed numbness of the bilateral feet and hands, followed by subacutely progressive weakness and amyotrophy of extremities. He became bed-ridden state, and dyspnea also appeared, so he was referred to our hospital. Physical examination revealed a lean man, with dark-reddish skin pigmentation, crabbed fingers, bilateral pretibial pitting edema, and bristles in extremities. Thoracoabdominal paradoxical respiration was observed and pulmonary vesicular sounds was decreased markedly in the both lungs. Laboratory data revealed hypoproteinemia, abnormalities of endocrine system, but M-protein was not detected. Serum vascular endothelial growth factor level was quite high. Chest radiography revealed elevation of the bilateral diaphragm, the % vital capacity (%VC) was 24%, and arterial blood gas analysis showed marked hypoxia with hypercapnia. These findings suggested that his respiratory failure was induced by bilateral diaphragmatic paralysis caused by bilateral phrenic nerve palsy due to Crow-Fukase syndrome. He became somnolent because of hypercapnic narcosis, so non-invasive positive pressure ventilation (NIPPV) was started. We treated him with intravenous immunoglobulin and oral corticosteroids therapies, and after these therapies, his symptoms were remarkably recovered and NIPPV became unnecessary soon. The most frequent causes of respiratory failure in Crow-Fukase syndrome are pleural effusion and pulmonary hypertension, and only two cases of this syndrome with respiratory failure caused by bilateral diaphragmatic paralysis were reported until now. When the patients with Crow-Fukase syndrome complain of dyspnea, we should take the diaphragmatic paralysis into consideration, which may be improved by appropriate therapies.     

Myopathy with trabecular fibers associated with familiar autoimmune polyglandular syndrome type 1

An association between limb-girdle muscular dystrophy and autoimmune polyglandular syndrome type 1 (APS1), in three sisters born to consanguineous parents, is presented. The components of APS1 in these patients were hypoparathyroidism, autoimmune adrenal insufficiency, primary hypogonadism and mucocutaneous candidiasis. A muscle biopsy performed on the first patient showed over 40 % of trabeculated fibers, suggesting the diagnosis of myopathy with trabeculated fibers (MTF). Intracranial calcification was found in the second patient; and epilepsy, and several other minor components of APS1, in the third; cataracts were found in the last two patients. The clinical manifestations and inheritance of MTF and APS1 are reviewed. While recessive mutations in the AIRE gene (21q22.3) cause APS1, genetic transmission of hereditary MTF has not been investigated in depth. Mutations in CRYAA, a gene that shares the same locus as AIRE, may cause recessive inheritance of cataracts. Thus, the proposal of this article is that linkage of contiguous genes that includes the AIRE gene, might be responsible for the association of both diseases in these three patients. Additional involvement of CRYAA, that possibly causes cataracts in two of the patients, might support this hypothesis, due to the proximity of this gene to AIRE. The genes COL6A1 and COL6A2, localized in 21q22.3, are discarded as transmitters of MTF in these cases, on clinical criteria. The authors wish to draw attention to the association between limb-girdle muscular dystrophy and APS1, since it has been very rarely reported in the medical literature.     

A patient with steroid responsive encephalopathy associated with autoimmune thyroiditis

We present a 58-year-old female with gradual cognitive decline and gait instability over 6 months. Her motor examination was notable for myoclonus, brisk reflexes with flexor plantar responses, and a cautious gait without ataxia. Cognitive testing revealed mildly impaired attention, but profoundly impaired calculation, judgment and visual memory. There were no manifestations of autoimmune thyroid disease. Routine laboratory analysis was unrevealing. Cerebrospinal fluid analysis was remarkable only for an elevated protein of 0.64 g/L (normal <0.45 g/L). Electroencephalography demonstrated intermittent bitemporal slowing. Brain MRI with gadolinium demonstrated extensive bilateral subcortical and periventricular white matter T2-weighted and hyperintensity on fluid attenuated inversion recovery MRI. Elevated anti-thyroperoxidase antibody of 8.07 IU/mL (<5.61 IU/mL) and thyroglobin antibody of 9.85 IU/mL (<4.11 IU/mL) were found and steroid responsive encephalopathy associated with autoimmune thyroiditis was diagnosed. Methylprednisolone (1 g daily for 3 days) resulted in dramatic improvement in cognition and mobility, which remained on follow-up.     

A young patient with endometrioid adenocarcinoma who suffered Trousseau's syndrome associated with vasculitis]

A 27-year-old woman was admitted to our hospital because of headache, fever and right neck pain. Neurological examination revealed mild meningeal signs, and hyper-reflexia in all extremities. In the laboratory tests, white-cell count was 13,000/mm3, rheumatoid factor(RF) and C-reactive protein(CRP) were positive. The cerebro-spinal fluid showed pleocytosis (56/mm3, neutorophils and lymphocytes were 26 and 28, respectively). Thus, she was diagnosed as aseptic meningitis. A few days later, she had weakness and dysesthesia of the right face and the left extremities. Pulse therapy with intravenous methylprednisolone was started. A magnetic resonance imaging (MRI) of the brain showed a hemorrhagic infarction in the right parietal lobe. In hemostatic markers, thrombin-antithrombin III complex(TAT; 106 ng/dl), D-dimer 1234 ng/dl, prothrombin fragment 1 + 2(F1 + 2; 2.36 nmol/L), beta-thromboglobulin (beta TG; 4,300 ng/dl) and platelet factor 4 (PF-4; 1,770 ng/dl) were extremely elevated. On duplex ultrasonography, a low echo lucent plaque was observed at the right internal carotid artery and the mean blood flow velocity in the right carotid artery was decreased. She was placed on oral prednisolone and warfarin for suspected stroke due to hypercoagulability associated with vasculitis. Afterwards, she discharged from our hospital. Two months later, she was readmitted to our hospital because of irregular menses and vaginal bleeding. Endometrial uterus biopsy was conducted, which revealed a grade I endometrioid adenocarcinoma. She was under total uterectomy without tumor recurrence. After the radical operation, white-cell count, RF, CRP, TAT, D-dimer, F1 + 2, and beta TG were normalized, and the mean flow velocity of the right common carotid artery was increased. Thereafter, she did not experience stroke recurrence. Therefore, we speculated that she had stroke due to hypercoagulability in association with malignancy, that is Trousseau's syndrome. We also assumed that aseptic meningitis, brainstem encephalitis associated with vasculitis in this patient are other clinical variants of paraneoplastic syndrome through immunological mechanisms associated with malignancy. We emphasize that patients with Trousseau's syndrome can be associated with other paraneoplastic manifestations such as vasculitis as seen in this patient.     

A case of Crow-Fukase syndrome showing improvement following excision and irradiation of bone lesions]

A 57-year-old woman suffering from pleural and pericardial effusion, pulmonary hypertention, lymphadenopathy, hepatosplenomegaly, edema, hypertrichosis, small hemangioma and polyneuropathy was diagnosed as Crow-Fukase syndrome. Osteoctomy of the left second rib and irradiation of this rib and the left iliac bone were performed. Serum vascular endothelial growth factor (VEGF) level decreased to less than one-half the level before the operation (from 5,180 to 2,150 pg/ml). Immediately after the operation, pleural and pericardial effusions due to hyperpenetration improved, and polyneuropathy and hypertrichosis due to hypervasularity also gradually improved. The resected lesion was histopathologically found to be of a plasmacytoma of the IgG lambda type. Since the level of VEGF in the tissue specimen was much lower (116 pg/ml) than that in the serum, VEGF could not have been produced by the plasmacytoma.     

Case of Isaacs' syndrome associated with Hashimoto disease]

We report a case of Isaacs' syndrome associated with Hashimoto disease. A 26-year-old woman, who had a past history of Hashimoto disease, complained of involuntary movements and muscle cramp in lower extremities. On examination, myokymia was seen in lower extremities. Myokymia was observed even during sleep, and worsened by exercise or bathing. The antibody against voltage-gated potassium channel (VGKC) was positive. Myokymic discharges were recorded with needle EMG in lower extremities. The patient was diagnosed as having Isaacs' syndrome. Isaacs' syndrome tends to be associated with some other autoimmune diseases. We discussed the correlation between Isaacs' syndrome and autoimmune disease. About 23% of Isaacs' syndrome cases are associated with some other autoimmune diseases and myasthenia gravis was most common. This is the first case report of Isaacs' syndrome associated with Hashimoto disease in Japan.     

Autonomic neuropathy associated with autoimmune disease

Mononeuropathy multiplex and mixed sensorimotor neuropathy are known complications of systemic vasculitis and related autoimmune disorders. Autonomic dysfunction is not generally considered a neurologic complication of these diseases. We report two patients who came to neurologic attention because of autonomic dysfunction and were then discovered to have autoimmune disease. Autonomic dysfunction may be the presenting sign of autoimmune disorders, which should be considered in the differential diagnosis of acquired autonomic disturbances.     

Dementia associated with toxic causes and autoimmune disease

Toxic causes of dementia include exposure to heavy metals such as lead, mercury and aluminum as well as to carbon monoxide and solvents. Autoimmune conditions include such entities as multiple sclerosis, systemic lupus erythematosus, Beh?et's disease and Sj?gren's syndrome. These conditions share broadly similar cognitive effects giving rise to impairments with subcortical features. Individuals are often affected at a relatively young age. Optimal preventative strategies include avoidance of toxic substances. Comprehensive neuropsychological assessment is valuable not only diagnostically and for monitoring but also to identify the patients' strengths and weaknesses, so that compensatory strategies can be recommended.     

A patient with Marfan''s syndrome and neurofibromatosis type 1 with polyneuropathy

Both Marfan's syndrome and neurofibromatosis type 1 are hereditary, autosomal dominant conditions. Here, we report the rare case of a patient fulfilling the clinical criteria for both diseases. In the absence of a family history of either of the two conditions, two independent de novo mutations are the most likely cause.     

A case of autoimmune polyglandular deficiency associated with progressive myopathy]

We reported a 29-year-old woman with autoimmune polyglandular deficiency (APGD) type 1 accompanied by progressive myopathy. She had chronic mucocutaneous candidiasis at the age of 3, primary hypothyroidism at 12, insulin dependent diabetes mellitus at 27, and adrenal insufficiency at 29 years. Laboratory findings indicated an underlying defect in cell mediated immunity. Meanwhile, she had progressive muscular weakness and wasting at the age of 22 years which brought her to our hospital at 29 years. On admission, she could not walk without support and raise her arms up to the level of shoulders. Moderate to severe muscle wasting as well as weakness was observed in the limb girdle muscles. Serum CK levels were mildly elevated. A needle EMG examination disclosed short-duration and low-amplitude polyphasic motor units at voluntary contraction with few fibrillations and positive sharp waves at rest. On muscle CT examination, decreased density was detected in the neck extensor, paravertebral, rectus femoris, vastus intermedius, biceps femoris and soleus muscles. Muscle biopsy was performed on the biceps brachii and rectus femoris muscles. The former showed chronic dystrophic changes including marked variation in fiber size with necrotic and degenerating process, interstitial fibrosis, and lobulated and right fibers. In the latter, in addition to variation in fiber size with some necrotic fibers and occasional multi-core structures, nemaline bodies were seen in approximately 30% of muscle fibers. The progressive muscle involvement in our patient might be induced from 1) endocrine abnormality, 2) autoimmune disorder, and/or 3) coincidental complication of nemaline myopathy or limb girdle muscular dystrophy. The clinical and laboratory examinations, however, failed to support any of them.(ABSTRACT TRUNCATED AT 250 WORDS)