Hemophagocytic lymphohistiocytosis with neurological presentation: MRI findings and a nearly miss diagnosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with rarer neurological presentation. When this occurs, diagnosis may be delayed. This report aims to call attention to clinical, laboratory, and radiological features that should prompt the correct diagnosis. A 13-year-old girl presented with progressive increase in intracranial pressure and ataxia. MRI showed a diffuse tumor-like swelling of the cerebellum with tonsillar herniation and patchy white matter post-contrast enhancement. Regression of swelling with steroids ruled out glioma and medulloblastoma, and brain lymphoma was considered. Diagnosis of HLH was reached 2 months after onset when uncontrolled fever and severe elevation of liver enzymes occurred. Two bone marrow biopsies were needed to demonstrate hemophagocytosis. Familial HLH was confirmed by perforin gene mutations. Bone marrow transplantation was performed. The early diagnosis of HLH may be life saving. Awareness of the disease is necessary to investigate its characteristic findings, thus avoiding a delay in diagnosis.     

Demyelinating peripheral neuropathy associated with hemophagocytic lymphohistiocytosis. An immuno-electron microscopic study

We report the case of an 11-year-old male who developed subacute diffuse polyradiculoneuropathy, associated with digestive symptoms and Epstein-Barr virus infection. Parental consanguinity was present. The laboratory findings including bone marrow smear were consistent with hemophagocytic lymphohistiocytosis (HLH). Electrophysiological study of peripheral nerves revealed an intense and diffuse demyelinating process. The histological nerve lesions were severe and purely demyelinating. Most axons were intact. There was a diffuse infiltration of the nerve parenchyma by mononuclear cells. Immuno-electron microscopic study evidenced entry of macrophages into Schwann cell cytoplasm with dissociation of myelin sheaths. This boy died several months after the onset of the neuropathic symptoms. HLH is a rare genetic or acquired disorder in childhood characterized by abnormal immune activation, which induces an uncontrolled inflammatory response with sustained hyperactivation of T lymphocytes and macrophages. Only very rare cases of peripheral nerve involvement have been described in HLH. This is the first case showing that peripheral nerves, as other viscera, may be destroyed by the macrophagic infiltration, which characterizes HLH.     

Spectrum of imaging appearances in Australian children with central nervous system hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder characterised by the proliferation and infiltration of lymphocytes and histiocytes. Central nervous system (CNS) infiltration is particularly devastating. Neuroradiological findings have been reported predominantly as individual case reports due to the rarity of the condition. To our knowledge there have been no published studies of imaging in Australian patients. This study aimed to retrospectively describe and illustrate the MRI appearances of CNS involvement by HLH in a cohort of seven Australian children from two paediatric centres between 2000 and 2011. MRI appearances demonstrate intersubject and intrasubject variability over time, likely reflecting the severity of CNS infiltration and associated demyelination. Familiarity with MRI patterns is important for assessing and monitoring disease activity.     

MRI and SPECT studies of dural arteriovenous fistulas presenting as pure progressive dementia with leukoencephalopathy: a cause of treatable dementia

We report two patients with dural arteriovenous fistulas (DAVFs) who presented with pure progressive dementia. Both patients showed only slowly progressive dementia, without headache, papilledema and other neurologic signs associated with diffuse white matter changes in MRI. MR cerebral angiography showed sigmoid sinus DAVFs that were mainly supplied by the occipital artery, together with retrograde filling of the superior sagittal and straight sinus and dilated cortical veins. SPECT studies showed extensive blood flow reduction in the occipital and parieto-occipital areas and right temporal lobe in one patient. Selective embolization for treatment of the DAVF improved cognitive function associated with the abnormal white matter MRI signal. MRI and SPECT showed that severity of dementia correlated with diffuse white matter changes and regional cerebral blood flow. Our cases suggest that gradually impaired cerebral circulation due to venous hypertensive encephalopathy could be involved in slowly progressive dementia with leukoencephalopathy resulting from a DAVF. DAVFs may be particularly important for differential diagnosis in elderly patients with pure progressive dementia. Thus, early diagnosis of DAVFs and treatment by endovascular surgery is important as treatable or reversible dementia.     

Severe cerebral involvement in adult-onset hemophagocytic lymphohistiocytosis

The diagnosis of hemophagocytic lymphohistiocytosis (HLH) with cerebral involvement is challenging given the rarity of HLH and its resemblance to the much more common severe sepsis. Timely diagnosis and treatment may be lifesaving. We report two cases demonstrating different and rare forms of severe brain involvement in adult patients with HLH: acute necrotizing encephalopathy, and diffuse hemorrhagic disease due to disseminated intravascular coagulation. Severe HLH with brain involvement in adults is rare. HLH with cerebral involvement should be considered in patients presenting with severe systemic inflammatory response syndrome (SIRS) but negative cultures and unusual or unexpectedly severe clinical and/or radiologic signs of cerebral dysfunction. Similar brain injury may occur in patients with cytokine storm syndrome due to COVID-19.BackgroundHemophagocytic lymphohistiocytosis (HLH) presents with fevers, rash, organomegaly, cytopenia, and increased triglycerides and ferritin (Ramos-Casals et al., 2014) [1]. Neurologic abnormalities are reported in about one-third of patients (Cai et al., 2017), including a few cases of acute necrotizing encephalopathy (ANE) (Xiujuan et al., 2015). Coagulation abnormalities are frequent in HLH patients (Valade et al., 2015).ObjectiveTo raise awareness about the importance of early diagnosis and treatment of HLH with neurological involvement to prevent serious complications and demise.     

Meningioma causing hyperostosis of the cranial convexity in a child

We present an 8-year-old girl with meningioma-associated hyperostosis. The patient was referred to our clinic due to headache and a frontoparietal midline swelling that was more prominent on the right side of the cranium. A cranial MRI revealed a frontoparietal parasagittal meningioma, accompanied by a diffuse hyperostosis, that appeared to extend extracranially. She underwent a right frontoparietal craniotomy and the tumor, together with the affected bone, was successfully removed. The histological examination confirmed meningioma (World Health Organization 2007 Grade 1) in the intracranial and extracranial lesions. Meningioma causing hyperostosis in a child is rare. The precise mechanism of hyperostosis associated with meningioma remains unclear; however, the most widely accepted theory is that the tumor invades the bone.     

Cerebral infarction secondary to vasospasm after perimesencephalic subarachnoid hemorrhage

Perimesencephalic subarachnoid hemorrhage (pSAH) has been described as a distinct form of subarachnoid hemorrhage (SAH) associated with good outcomes. We report a 48-year-old female who developed cerebral infarction due to severe diffuse vasospasm following pSAH. The patient presented with non-aneurysmal pSAH and was discharged home on day 5. However, one week later she developed an acute onset of right hemiparesis. A brain MRI showed acute infarctions on diffusion weighted imaging and her cerebral angiogram showed diffuse vasospasm. The patient received intra-arterial diltiazem and hypervolemic-hypertensive-hemodilution therapy with resulting resolution of the vasospasm and hemiparesis. While not as common as in SAH, there is a potential for the occurrence of cerebral infarction due to vasospasm after pSAH.     

A hypermotor seizure with a focal orbital frontal lesion originating in the insula: a case report

We present herein the case of a patient with a focal orbital frontal lesion on magnetic resonance imaging (MRI), but an insular onset of seizures. A 15-year-old boy suffered from hypermotor seizures for 9 years. In his seizures, he initially had a sensation that sounds were distant, and then his consciousness became impaired. After a short period of tonic activity, violent activities occurred, such as kicking or gripping some objects and shaking. MRI showed a focal cortical abnormality in the right orbital frontal lobe. [(18)F]FDG-PET revealed diffuse hypometabolism in the right frontal lobe, especially in the same site as the cortical lesion on MRI. The seizure onset zone was localized in the right anterior insula by intracranial recording. A resection of the right anterior insula and a partial disconnection of the frontal lobe were performed, rendering the patient seizure-free.     

Post-partum cerebral angiopathy: repetitive TCD,MRI, MRA,and EEG examinations

We report of a woman with post-partum cerebral angiopathy (PCA), in whom we repetitively performed transcranial Doppler sonography (TCD), MR imaging (MRI), and MR angiography (MRA) to evaluate the underlying pathophysiology. A 31-year-old woman, Gemini pregnant, complained of severe throbbing frontal headache four days after an uneventful delivery by Cesarean section. Blurred vision occurred eight days after delivery, followed by three generalized tonic-clonic seizures. Neurological examination revealed a somnolent woman without focal neurological deficits. At the day of the seizures increased flow velocities and disturbed flow were observed in the right posterior and anterior cerebral artery on transcranial Doppler (TCD). MRI showed infra- and supratentorial patchy hyperintensities in T2-weighted images and in the FLAIR sequence. Diffusion-weighted imaging revealed corresponding multi-focal hyperintense areas indicating increased diffusion and MRA showed a diffuse multisegmental narrowing of all pial arteries. MRI at day 10 was completely normal, but MRA still revealed vascular narrowing in the right posterior cerebral artery. General slight flow accelerations in all basal arteries occurred after 10 days and lasted for three weeks. PCA is apparently associated with a vascular narrowing causing cerebral ischemia with increased diffusion. Later reactive cerebral hyperperfusion is observed. Vascular narrowing and cerebral hyperperfusion still persist after MRI has normalized.     

An autopsy case of primary central nervous system lymphoma with diffuse intracerebral lesion]

A case of primary central nervous system lymphoma (PCNSL) who initially showed clinical pictures like encephalitis and diffuse lesions on MRI was reported, including postmortem pathologic examinations. A 68-year-old woman was seen in March, 1990 with a 1-month history of the progressive gait disturbance. She was very unstable and could barely stand by herself, though she did not show any focal neurologic deficits. She showed no evidence of systemic diseases. The cerebrospinal fluid analysis was normal. T2-weighted image of MRI demonstrated the diffuse symmetric hyperintense lesions mainly in the periventricular white matter. The progressive intellectual decline and the spasticity of four limbs developed as the diffuse lesions on MRI gradually extended. Despite the administration of corticosteroids under the presumptive diagnosis of PCNSL, she rapidly fell into the apallic syndrome within two months. Her EEG showed periodic synchronous discharges. Three months later, she suddenly developed signs of right uncal herniation. CT showed a large mass lesion in the right hemisphere. After the anti-edema therapy, signs of herniation regressed. The serial CT scans demonstrated a gradual decrease in the mass effect, while another multi-nodular lesions appeared and then disappeared one after another bilaterally. Eventually, the diffuse low densities in the cerebral white matter and the ventricular enlargement had remained. She died of bronchopneumonia eight month after the onset of symptoms. The clinical importance of the diagnosis of PCNSL which initially shows diffuse symmetric lesions without a mass is stressed. Postmortem examinations revealed PCNSL, diffuse, large cell type according to the Lymphoma Study Group classification. The lymphoma cells were proved to be B cell origin from the immunohistochemical study of frozen tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intracranial Vasculitis and Multiple Abscesses in a Pregnant Woman

Cerebral vasculitis is an unusual disorder with many causes. Infectious causes of cerebral vasculitis are predominantly bacterial or viral in nature. Purulent bacterial vasculitis is most often a complication of severe bacterial meningitis. The patient is a 25-year-old African American female, 25 weeks pregnant, who presented to the neurology service after a consult and referral from an outside hospital. She had a 1-month history of right sixth nerve palsy. Initial workup included a negative lumber puncture and a noninfused magnetic resonance imaging (MRI). Three days later, the patient developed right-sided migraine headaches and right third nerve palsy. The angiogram revealed diffuse irregularity and narrowing of the petrous, cavernous, and supraclinoid portions of the internal carotid and right middle cerebral arteries. Shortly thereafter, an MRI examination revealed diffuse leptomeningeal enhancement and abscess and a right parietal subdural empyema. Infectious vasculitis secondary to purulent meningitis has a rapidly progressive course and presents with cranial nerve palsy with involvement of the cavernous sinus. Although the association of this disease with pregnancy has not been established, it should be recognized that the early imaging studies may be negative or discordant and follow-up imaging might be necessary.     

Neurologic validity of the Wisconsin Card Sorting Test with a pediatric population

This study investigated the neurologic validity of the Wisconsin Card Sorting Test (WCST) with a pediatric population; that is, the ability of the test to detect dysfunction in the frontal lobes. Fifty children with diverse etiologies of brain dysfunction were classified via EEG, MRI, or CT as having left hemisphere, right hemisphere, or bilateral frontal, extrafrontal, or multifocal/diffuse regions of brain dysfunction. Findings failed to support the hypotheses that WCST performance is more impaired in frontal lesions than extrafrontal or multifocal/diffuse lesions, or that WCST performance is more impaired in left hemisphere lesions than right. Although the WCST is not helpful in localizing cerebral area of dysfunction, it may still be a clinically useful test for examining processes that children use to solve complex problems.     

Diffuse white matter changes caused by dural arteriovenous fistula.

We present two patients with progressive dementia who showed diffuse white matter changes on magnetic resonance imaging (MRI) associated with dural arteriovenous fistula (DAVF) involving the transverse-sigmoid sinuses. Angiography of both patients revealed that DAVF was associated with multiple occlusive changes in the dural venous sinus. The associated occlusive changes isolated the straight sinus and the DAVF from the other venous sinuses, and concentrated the drainage of the DAVF in the straight sinus. We postulate that the venous hypertension of the straight sinus resulted in the venous ischemia of the white matter, diffuse white matter changes on MRI, and progressive neurological signs including dementia. Treatment of the DAVF reversed white matter changes and neurological signs. Associated with the venous sinus occlusions, the DAVF caused dementia with diffuse white matter changes due to the venous ischemia.     

A case of postural and kinetic tremor caused by diffuse axonal injury]

We reported a 25-year-old woman with postural and kinetic tremor caused by diffuse axonal injury. The patient demonstrated consciousness disturbance, left oculomotor palsy and tetraparesis because of an automobile accident. T2-weighted and FLAIR MRI showed features of diffuse axonal injury. Hyperintense lesions appeared in the corpus callosum, fornix, dorsal portion of midbrain, right cerebral peduncle, and bilateral internal capsules. About 3 weeks later, head tremor and left hemiparesis appeared with improvement of consciousness. Administration of trihexyphenidyl decreased the tremor. Ten weeks after the accident, a coarse tremor in the head and right upper extremity developed after withdrawal of trihexyphenidyl. Tremor in the right upper limb predominantly occurred while maintaining an upright posture and with intended movements. Re-administration of trihexyphenidyl decreased the tremors. The dentatothalamic pathway is one of the lesions responsible for posttraumatic tremor. Our patient demonstrated lesions of diffuse axonal injury involving the dentatothalamic pathway. We considered that these lesions were associated with postural and kinetic tremor in our case. The tremor occurred at least 3 weeks after the accident. This finding suggested that the tremor was caused by transsynaptic alternations of thalamus or the extrapyramidal system secondary to involvement of the dentatothalamic pathway.     

Neurologic Validity of the Wisconsin Card Sorting Test with a Pediatric Population

This study investigated the neurologic validity of the Wisconsin Card Sorting Test (WCST) with a pediatric population; that is, the ability of the test to detect dysfunction in the frontal lobes. Fifty children with diverse etiologies of brain dysfunction were classified via EEG, MRI, or CT as having left hemisphere, right hemisphere, or bilateral frontal, extrafrontal, or multifocal/diffuse regions of brain dysfunction. Findings failed to support the hypotheses that WCST performance is more impaired in frontal lesions than extrafrontal or multifocal/diffuse lesions, or that WCST performance is more impaired in left hemisphere lesions than right. Although the WCST is not helpful in localizing cerebral area of dysfunction, it may still be a clinically useful test for examining processes that children use to solve complex problems.     

Cerebellar ataxia and leukoencephalopathy associated with cobalamin deficiency

We report a patient who presented progressive cerebellar ataxia associated with vitamin B(12) deficiency. Brain magnetic resonance imaging (MRI) demonstrated a diffuse leukoencephalopathy. Six months after the initiation of methylcobalamin therapy, there were clinical improvement and reduction in the MRI abnormalities.     

Spontaneous intracranial hypotension with pachymeningeal enhancement on MRI.

Spontaneous intracranial hypotension (SIH) is a rarely reported syndrome of spontaneously occurring postural cephalalgia associated with low CSF pressure. We report a case of SIH in which MRI of the brain revealed diffuse symmetric pachymeningeal enhancement that resolved without specific therapy.     

Comparison of magnetic resonance imaging with neuropathological findings in the diagnosis of HIV and CMV associated CNS disease in AIDS.

OBJECTIVES: To compare the results of clinical assessment and MRI with neuropathological findings in the diagnosis of HIV and cytomegalovirus (CMV) associated CNS disease. METHODS: A retrospective study of 35 patients infected with HIV who were examined at necropsy between four and 70 (median 20) days after neurological assessment and MRI. RESULTS: Of the 35 patients, 19 had diffuse white matter hyperintensity on T2 weighted MRI, six of whom also had focal lesions. Nine other patients had focal white matter lesions and seven had changes in cortical atrophy only. Necropsy in the 19 with diffuse white matter hyperintensity showed HIV leukoencephalopathy (HIVLEP) with encephalitis in 10, CMV encephalitis in three, both HIVLEP/HIV encephalitis and CMV encephalitis in one, lymphoma in three, and non-specific inflammation in two. Necropsy in the 16 other patients without diffuse white matter hyperintensity showed CMV encephalitis in six, HIV encephalitis (without HIVLEP) in two, CMV encephalitis and HIVLEP/HIV encephalitis in one, non-HIV associated abnormalities in five, herpes simplex encephalitis in one, and lymphoma in one. CMV DNA was detected in CSF of five of seven patients with CMV encephalitis and in two of two with CMV associated polyradiculopathy but without CMV encephalitis. Diffuse white matter hyperintensity on MRI had a sensitivity of 100%, a specificity of 66.6%, and a positive predictive value of 58% for diagnosis of HIVLEP. CONCLUSION: Diffuse white matter hyperintensity on MRI can be due to either HIV or CMV associated pathology or non-specific abnormalities.     

Prediction of short-term neurological outcome in full-term neonates with hypoxic-ischaemic encephalopathy based on combined use of electroencephalogram and neuro-imaging

BACKGROUND: In infants with hypoxic-ischaemic encephalopathy (HIE), prediction of the prognosis is based on clinical, neuro-imaging and neurophysiological parameters. METHODS: EEG, cranial ultrasound, MRI and follow-up findings of 23 infants (GA 35-42 weeks) with HIE were studied retrospectively to assess 1) the contribution of ultrasound, MRI and EEG in predicting outcome, 2) the accuracy of ultrasound as compared to MRI, and 3) whether patterns of brain damage and EEG findings are associated. RESULTS: An abnormal EEG background pattern was highly predictive of adverse outcome [positive predictive value (PPV) 0.88]. If combined with diffuse white and deep and/or cortical grey matter changes on ultrasound or MRI, the PPV increased to 1.00. Abnormal neuro-imaging findings were also highly predictive of adverse outcome. Abnormal signal intensity in the posterior limb of the internal capsule, and diffuse cortical grey matter damage were associated with adverse outcome. MRI showed deep grey matter changes more frequently than ultrasound. Severely abnormal neuro-imaging findings were always associated with abnormal EEG background pattern. CONCLUSIONS: Both early EEG and neuro-imaging findings are predictive of outcome in infants with HIE. The predictive value of EEG is strengthened by neuro-imaging.     

Neuropsychological Assessment in a Case of Adult-Onset Hemophagocytic Lymphohistiocytosis (HLH)

We present a case of an individual diagnosed with hemophagocytic lymphohistiocytosis (HLH), an extremely rare and commonly fatal disorder characterized by rapid dysregulation of immune system processes. Typical age of onset is in childhood, with adult-onset occurring less frequently. The pathophysiology of this condition is characterized by a hyperinflammatory response with infiltration of visceral organs, lymph nodes, bone marrow, and the central nervous system. The clinical presentation has been documented in the extant medical literature. However, there appear to be no published reports of neuropsychological functioning in HLH patients. The patient we present here is a 28-year-old woman with 16 years of education who developed HLH subsequent to systemic lupus erythematosus flare-up. She was initially comatose for 3 weeks. Acute MRI reported multiple subcortical abnormalities, including the brainstem. The patient underwent chemotherapy, immunosuppresant, and steroid treatments. She underwent a neuropsychological evaluation at 2.5 and 7 months post initial presentation. Preliminary neuropsychological evaluation found impairments in motor abilities and aspects of executive functions. Subsequent evaluation showed improved executive function and relative sparing of higher-order cognitive abilities, but continued impairment on motor tests. To our knowledge this is the first study to report neuropsychological data for an adult diagnosed with HLH.