Rapid Neurological Deterioration Research Articles

Childhood X-linked Adrenoleukodystrophy: Clinical-Pathologic Overview and MR Imaging Manifestations at Initial Evaluation and Follow-up

X-linked adrenoleukodystrophy (ALD) is a rare metabolic disorder caused by peroxisomal enzyme failure. Several phenotypes can be distinguished on the basis of clinical onset and manifestations. Childhood cerebral X-linked ALD is the most severe phenotype, resulting in rapid neurologic deterioration and early death. Patients with this disease may be hospitalized with far-advanced central nervous system (CNS) lesions or may complain of symptoms similar to those of certain psychiatric disorders, possibly leading to a wrong diagnosis. Although the general prognosis for patients with childhood cerebral X-linked ALD is still poor, new treatment modalities have been introduced, some of which are helpful in relieving clinical symptoms and prolonging life. With the introduction of these new therapies and increased clinical detection of childhood cerebral X-linked ALD, brain magnetic resonance (MR) imaging has become an essential tool for initial and follow-up evaluation. MR imaging allows early detection of CNS lesions and helps differentiate childhood cerebral X-linked ALD from other disorders. The characteristic MR imaging features of childhood cerebral X-linked ALD have been well documented, although most radiologists have limited experience with serial follow-up MR imaging in this context. Familiarity with the clinical-pathologic manifestations and progressive MR imaging features of childhood cerebral X-linked ALD will be helpful in evaluating affected patients.

Fright is a provoking factor in vanishing white matter disease

Leukoencephalopathy with vanishing white matter is an inherited disorder with a chronic progressive disease course and additional episodes of rapid neurological deterioration. These episodes typically are provoked by febrile infections or minor head trauma. We report on two patients who experienced an episode of rapid neurological deterioration after a fright.

Transmission of rabies virus from an organ donor to four transplant recipients

In 2004, four recipients of kidneys, a liver, and an arterial segment from a common organ donor died of encephalitis of an unknown cause. We reviewed the medical records of the organ donor and the recipients. Blood, cerebrospinal fluid, and tissues from the recipients were tested with a variety of assays and pathological stains for numerous causes of encephalitis. Samples from the recipients were also inoculated into mice. The organ donor had been healthy before having a subarachnoid hemorrhage that led to his death. Encephalitis developed in all four recipients within 30 days after transplantation and was accompanied by rapid neurologic deterioration characterized by agitated delirium, seizures, respiratory failure, and coma. They died an average of 13 days after the onset of neurologic symptoms. Mice inoculated with samples from the affected patients became ill seven to eight days later, and electron microscopy of central nervous system (CNS) tissue demonstrated rhabdovirus particles. Rabies-specific immunohistochemical and direct fluorescence antibody staining demonstrated rabies virus in multiple tissues from all recipients. Cytoplasmic inclusions consistent with Negri bodies were seen in CNS tissue from all recipients. Antibodies against rabies virus were present in three of the four recipients and the donor. The donor had told others of being bitten by a bat. This report documenting the transmission of rabies virus from an organ donor to multiple recipients underscores the challenges of preventing and detecting transmission of unusual pathogens through transplantation.

Management of Epidural Abscesses and Subdural Empyemas

Epidural abscesses (EA) and subdural empyemas (SE) are intracranial infections that occur in the potential spaces between the skull and brain. Both are most commonly caused by direct extension of infection from sinus disease or by contamination incurred during craniotomy. Patients can manifest a spectrum of clinical symptoms ranging from subtle changes postoperatively to rapid neurological deterioration associated with fever. Diagnosis is confirmed with computed tomography or magnetic resonance imaging with contrast. Urgent surgical treatment is usually indicated because both are potentially life-threatening conditions. Empirical antibiotic therapy, followed by tailoring of therapy after identification of the organism, is an absolute necessity. Because improved patient outcomes are associated with early detection and prompt treatment of epidural abscesses and subdural empyemas, physicians should have a high level of suspicion for their presence and pursue their diagnosis and treatment expeditiously.

Spontaneous Hemorrhage of a Spinal Ependymoma: A Rare Cause of Acute Cauda Equina Syndrome

An interesting case of spontaneous bleeding from an ependymoma of the filum terminale is presented. To document a rare case of rapid neurologic deterioration as a consequence of spinal tumoral hemorrhage and to highlight important issues regarding tumor histologic subtype and the impact of anticoagulation that have emerged from an illuminating review of the literature. To our knowledge, there have been only 8 reported cases of hemorrhage from an ependymoma of the filum terminale or conus medullaris causing acute cauda equina syndrome. Bleeding is described in the pathology texts as being a consequence of the vascular architecture of the myxopapillary subtype and so postulated to be more common in this group. Anticoagulation is recognized to increase the frequency of tumoral bleeding, but no studies report its effect of severity of clinical presentation. We report the case of a 57-year-old woman who developed nontraumatic acute cauda equina syndrome, including sphincter compromise. She underwent a lumbosacral laminectomy for evacuation of a hematoma, at which stage a filum terminale ependymoma was excised. Histopathologic analysis demonstrated it to be of a nonmyxopapillary subtype. The patient demonstrated gradual improvement of the neurologic deficit. At 12-month follow-up, her saddle area sensory deficit has resolved, her right lower limb is much stronger allowing her to walk long distances, and she is successfully performing intermittent self-catheterization of her bladder. The possibility of an underlying tumor should always be borne in mind so that adequate preoperative planning can be undertaken. The presence of the myxopapillary subtype should not prevent a clinician from excluding other reasons for hemorrhage, and counseling when reinstituting anticoagulation must include warning against a worse prognosis from any future hemorrhage.

Hematomas subdurales de causa aneurismática: estrategia terapéutica sin angiografía diagnóstica

Ruptured aneurysms on rare occasions cause subdural hematomas as described in literature. Sudden deterioration and coma is a common feature in those patients and a emergent surgical attitude is prompt required, even without confirmation with angiography.We described three cases with acute subdural hematomas and little or no subarachnoid hemorrhage caused by ruptured aneurisms who presented with rapid neurologic deterioration. Urgent craniotomy and evacuation of the hematoma was performed without previous angiography in the three patients. In two patients the aneurysm was found during surgical exploration and subsequently clipped; in the remaining patient the aneurysm was embolized postoperatively.The occurrence of a subdural hematoma caused by the rupture of an intracranial aneurysm must be suspected in spontaneous subdural hematomas, especially in association with disproportioned conscious deterioration. All the three patients we report debuted with sudden conscious deterioration. If a ruptured aneurysm causing subdural hematoma is suspected, early surgical intervention is required even if angiography is not available. Severe neurological deficit and uncal herniation might still be reversible if provided decompression can be carried out in promptly. Angiography availability should not postpone surgery. Aneurysm presence should be ruled out whether by surgical exploration or by delayed angiography. Posterior communicating aneurysm are related to formation of subdural hematoma.

Med-18. Rapid Neurologic Deterioration in a Patient with Herpes Simplex in the Presence of Negative Neuroimaging.

med-18. Rapid Neurologic Deterioration in a Patient with Herpes Simplex in the Presence of Negative Neuroimaging.

Retrospective analysis of spinal missile injuries.

One hundred six patients with spinal missile injury from war zones were admitted to our department from 1994 to 2000. Functional recovery and complications in surgical and conservative treatment groups were evaluated. Sixty-five were treated surgically, of whom 55 (84%) had incomplete injuries (Frankel scores B, C, and D). In the conservative group, 28 (68%) had incomplete injuries. A total of 81 patients (53 in the surgical group, 28 in the conservative group) could be monitored for functional recovery. In the surgical group, 34 (64%) showed improvement, 15 (28%) were unchanged, and four (7%) worsened. In the conservative group, 17 (60%) improved, nine (32%) remained unchanged, and two (7%) worsened. Cerebrospinal fluid fistula was observed in ten patients, seven of them in the surgically treated group. Five of seven meningitides were seen in the surgically treated group. Surgical intervention is not essential for spinal gunshot injury; however, it may be beneficial for patients with CSF fistula, infectious and compressing foreign bodies in the injury site, instability, and rapid neurological deterioration.

Treatment of neuroblastoma with intraspinal extensions.

Neuroblastoma is the most common malignant cause of spinal compression in the paediatric population. Chemotherapy is commonly considered as the first-line treatment for these patients. The role of neurosurgical decompression and radiotherapy are still controversial. Thirteen children diagnosed as having neuroblastoma with intraspinal extension were included in this report. All patients presented with neurological deficits and were treated with chemotherapy initially, after which 3 patients recovered, 4 improved and 6 were aggravated into paraplegia. Two of the 6 aggravated patients received emergent laminectomy with removal of intraspinal tumour and recovered satisfactorily. Although spread of tumour into the spinal canal indicates an advanced disease, aggressive treatments such as chemotherapy and surgical resection can often improve neurological symptoms and life quality. Neurological decompression is recommended for patients with intraspinal neuroblastoma and rapid neurological deterioration during chemotherapy.

Rapid neurological deterioration associated with minor head trauma in chronic hydrocephalus

Rapid neurological deterioration associated with minor head trauma in chronic hydrocephalus

Rapid neurological deterioration associated with minor head trauma in chronic hydrocephalus

Rapid neurological deterioration associated with minor head trauma in chronic hydrocephalus

Late-onset multiple sclerosis.

The onset of multiple sclerosis (MS) after age 50 is infrequent and presents a diagnostic challenge. The purpose of the present study was to review the prevalence, presentation, and clinical characteristics of late-onset MS. A retrospective chart review. The Multiple Sclerosis Center at Sheba Medical Center, Israel. 640 patients with a definite diagnosis of MS. Diagnosis of MS was established according to Poser criteria and confirmed by brain magnetic resonance imaging (MRI) using our unit's computerized database. Late-onset MS was defined as the first presentation of clinical symptoms after the age of 50 years. For each patient, age, gender, clinical presentation, disease course, neurological involvement, disease duration, neurological disability assessed, and Progression Index (PI) were analyzed. All patients were interviewed using the structured clinical interview for DSM-IV, SCID-lifetime Hebrew version. Of 640 MS patients, 30 (4.6%) were diagnosed as suffering from late-onset MS. Mean age at onset was 53.5 +/- 3.1, range 50 to 62 years. Female to male ratio was 1.73:1. Mean disease duration was 7.6 years, range 2 to 11 years. In 50% of patients the disease course was relapsing-remitting. Motor symptoms were the most common neurological presentation at onset (63.3%). Major depressive episode was diagnosed in 6 out of 30 patients (20%) in the two years prior to the diagnosis of MS. After a mean disease duration of 7.6 years there was a marked increase in sphincteric and cerebellar involvement. In addition 7 out of 30 patients had suffered a major depressive episode within 4 years of diagnosis. Mean PI was 0.81, suggesting rapid neurological deterioration. Late-onset MS is not rare and may present as major depression and, although neurological presentation at onset is similar to that of young adults, progression to disability is more rapid and a primary progressive course is more prevalent.

Forma de debut neurológico de la linfohistiocitosis hemofagocítica

Haemophagocyte lymphohistiocytosis (HLH) is a hematological disorder, autosomal recessive and in which there is benign proliferation of histiocytes with intense phagocytic activity of hematopoietic cells. The clinical features include fever, pancytopenia, coagulation disorders, liver dysfunction, the presence of histiocytes and haemophagocytes in the bone marrow, lymph nodes, spleen and liver. The nervous system is always involved and sooner or later patients develop a nervous system disorder with variable symptoms which may include irritability, disorders of consciousness, convulsions, ataxia, nystagmus or signs of intracranial hypertension. Onset of the disease showing purely neurological features is rare. We therefore describe the case of an 8 month old baby with HLH with a purely neurological condition involving irritability, horizontal rapid eye movements and vertical saccadic movements of both eyes and focal convulsive seizures. Initial complementary examinations were normal, except for study of the CSF with a lowered protein level and cells (monocytes). Finding hepatosplenomegaly and pallor, together with the laboratory investigations, made it advisable to do a bone marrow punch biopsy to detect haemophagocytes which would be diagnostic of HLH. In spite of chemotherapy there was rapid neurological deterioration, with alterations of the white matter and hydrocephaly which required insertion of a ventriculo-peritoneal shunt. The patient died when he was 10 months old. The cases of HLH in which cerebromeningeal disorders alone precede systemic symptoms are extremely rare. Hence the interest in reporting this case, so that it may be borne in mind in other cases of acute neurological onset. In this case initially there was encephalitis alone, but this was rapidly followed by systemic complications.

Extracranial Aneurysms of the Posterior Inferior Cerebellar Artery

Objective: Extracranial aneurysms of the distal posterior inferior cerebellar artery (PICA) are extremely rare and sometimes difficult to diagnose without an adequate angiogram. We present the first series of 3 patients who were evaluated by the senior author and treated surgically. Methods and Results: All 3 patients presented with subarachnoid hemorrhage (SAH). Clincial symptoms, included occipital headache, nuchal rigidity, abducens nerve palsy and rapid neurologic deterioration. A unilateral injection of the vertebral artery failed to show the distal contralateral PICA and the aneurysm in 1 patient. All patients underwent aneurysm clipping through a posterior fossa craniectomy and C-1 laminectomy. The aneurysms were located on the tonsillomedullary segment of the PICA, 10–12 mm below the level of the foramen magnum. Conclusions: It is important to adequately visualize the distal extent of both PICAs or these aneurysms may not be seen. Patients who present with SAH must have the entirety of both vertebral arteries evaluated to avoid missing these aneurysms. The aneurysms were located adjacent to the atlas necessitating an upper cervical laminectomy for adequate surgical exposure. In general, the patients did well postoperatively and none of the patients developed cerebral vasospasm.

Neoplastic meningitis: diagnosis and treatment considerations.

Neoplastic meningitis is an increasingly recognized complication of advanced metastatic cancer and, if left undiagnosed or untreated, is characterized by rapid neurologic deterioration and death. Thus, the diagnosis and treatment of neoplastic meningitis present challenges for the clinical oncologist. The diagnosis of neoplastic meningitis is based on clinical signs and symptoms, laboratory analysis of cerebrospinal fluid to determine cell count and cytology, and analysis of neuroimaging studies for evidence of leptomeningeal or cranial nerve enhancement. Once diagnosed, conventional treatment regimens may include radiotherapy combined with systemic or intrathecal chemotherapy, often with the antimetabolites cytarabine and/or methotrexate. However, the prognosis for neoplastic meningitis secondary to an underlying solid tumor or recurrent leukemia is poor with conventional treatment regimens. Therefore, novel agents for intrathecal administration, including DepoCyttrade mark, mafosfamide, and topotecan, or novel therapeutic approaches, including conjugated monoclonal antibodies and immunotoxins or gene therapy, are currently under investigation. Such new agents and therapeutic approaches will facilitate the development of effective treatment strategies and will ultimately improve the outcome for patients with this devastating disease. This article provides an overview of the approaches to the diagnosis, evaluation, and treatment of neoplastic meningitis.

Is decompressive craniectomy for acute cerebral infarction of any benefit?

BACKGROUND Acute occlusion of the major cerebral arteries results in ischaemic changes to the brain, without time for reperfusion by the collateral circulation. The subsequent cellular events lead to a breakdown of the blood-brain barrier, causing malignant cerebral edema manifested clinically by a rapid neurological deterioration. The aim of this study was to determine the value of surgical decompression in patients who present with acute cerebral infarction. METHODS Retrospective review of patients with deteriorating consciousness level from massive cerebral ischemia and secondary edema, treated by decompressive craniectomy. RESULTS There were 10 patients over a 2-year period from 1997–99, consisting of seven male and three female patients (mean age 47.56 years) with a mean preoperative Glasgow Coma Scale (GCS) score of 6/15. Three patients had dominant middle cerebral artery (MCA) infarction, four had nondominant MCA infarction, one had posterior cerebral artery infarction, and the remaining two had cerebellar infarction. At a mean follow-up period of 7 months, two patients had died (20% mortality), four patients (40%) were vegetative or severely disabled, and the remaining four patients (40%) had mild disability or good outcome. Favorable prognostic factors were younger age (less than 50 years) and good initial GCS score (14 or better). CONCLUSION Decompressive craniectomy in the setting of acute brain swelling from cerebral infarction is a life-saving procedure and should be considered in younger patients who have a rapidly deteriorating neurologic status.

Spinal cord astrocytomas: presentation, management and outcome.

Intramedullary spinal cord astrocytomas are uncommon tumors. They are the most common spinal cord tumor in children and in adults are second only to ependymomas in frequency of occurrence. Low-grade histology predominates with high-grade lesions comprising only ten to fifteen percent of pediatric tumors and a slightly higher proportion in adults. Presenting symptoms typically evolve over months to years with regional back pain the most commonly reported initial complaint. Malignant tumors produce rapid neurological deterioration. MRI is the diagnostic modality of choice: spinal cord astrocytomas are iso- to slightly hypointense on T1, hyperintense on T2 and commonly have associated cysts. They enhance less intensely and are more eccentric than ependymomas. The goals of surgical intervention are to obtain a tissue diagnosis and resect as much tumor as possible without adversely affecting neurological function. Astrocytomas are infiltrating neoplasms and total resection is not generally possible. Somatosensory and motor evoked potential monitoring are routinely used but it is unclear if they improve outcomes. The operating microscope and bipolar cautery are essential surgical tools; the ultrasound and ultrasonic surgical aspirator are useful surgical adjuncts. Laminectomy is performed on adults while laminoplasty is favored for pediatric patients. Outcome for low-grade astrocytomas is less favorable than that of ependymomas with regard to both recurrence and function though many have prolonged survival. There is no correlation of extent of resection and recurrence. Outcome for high-grade tumors is extremely poor; tumor progression is relentless; median survival is thirteen months in children and six months in adults.

Cerebral fluorine-18 fluorodeoxyglucose positron emission tomographic findings in x-linked adrenoleukodystrophy.

Fluorine-18 fluorodeoxygluc (F-18 FDG) scan findings are reported in a 10-year-old boy with X-linked adrenoleukodystrophy (X-ALD) who was evaluated for progressive encephalopathy, which is characteristic of the disease. The brain MRI study showed typical white matter abnormalities in the parietal and occipital lobes. The subsequent F-18 FDG revealed hypometabolic activity in the cerebral cortex, most prominently in the occipital lobes and particularly in the visual cortex. There was evidence of a gradient of diffusely increased glucose metabolism in most of the cerebral white matter. These changes were most prominent in the parietal and temporal lobes and less marked in the occipital areas. The functional changes demonstrated by the F-18 FDG scan were more extensive than the structural abnormalities demonstrated by MRI and better correlated with the the patient's rapid neurologic deterioration. Brain F-18 FDG positron emission tomographic (PET) imaging is helpful in the accurate delineation of the involved areas and in monitoring the progression of the demyelinating process in the different stages of this disease. The results also suggest that F-18 FDG PET may be useful in detecting demyelinating diseases associated with inflammation.

Mutational analysis and genotype-phenotype correlation of 29 unrelated Japanese patients with X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is an inherited disease characterized by progressive neurologic dysfunction, occasionally associated with adrenal insufficiency. The classic form of ALD usually has onset in childhood (childhood cerebral ALD), with rapid neurologic deterioration leading to a vegetative state. Adult-onset cerebral ALD also presents with rapidly progressive neurologic dysfunction. Milder phenotypes such as adrenomyeloneuropathy and Addison disease only also have been recognized. Despite discovery of the causative gene, a molecular basis for the diverse clinical presentations remains to be elucidated. To conduct mutational analyses in 29 Japanese patients with ALD from 29 unrelated families, to obtain knowledge of the spectrum of mutations in this gene, and to study genotype-phenotype correlations in Japanese patients. The 29 patients comprised 13 patients with childhood cerebral ALD, 11 patients with adult-onset cerebral ALD, and 5 patients with adrenomyeloneuropathy. We conducted detailed mutational analyses of 29 unrelated Japanese patients with ALD by genomic Southern blot analysis and direct nucleotide sequence analysis of reverse transcriptase-polymerase chain reaction products derived from total RNA that was extracted from cultured skin fibroblasts, lymphoblastoid cells, or peripheral blood leukocytes. Three patients with adult-onset cerebral ALD were identified as having large genomic rearrangements. The remaining 26 patients were identified as having 21 independent mutations, including 12 novel mutations resulting in small nucleotide alterations in the ALD gene. Eighteen (69%) of 26 mutations were missense mutations. Most missense mutations involved amino acids conserved in homologous gene products, including PMP70, mALDRP, and Pxa1p. The AG dinucleotide deletion at position 1081-1082, which has been reported previously to be the most common mutation in white patients (12%-17%), was also identified as the most common mutation in Japanese patients (12%). All phenotypes were associated with mutations resulting in protein truncation or subtle amino acid changes. There were no differences in phenotypic expressions between missense mutations involving conserved amino acids and those involving nonconserved amino acids. There are no obvious correlations between the phenotypes of patients with ALD and their genotypes, suggesting that other genetic or environmental factors modify the phenotypic expressions of ALD.

Photoparoxysmal response in late infantile neuronal ceroid-lipofuscinosis

A patient presented with rapid developmental regression whose MRI findings suggested a leukodystrophy, but nerve, muscle, skin, and bone marrow biopsies were unrevealing. A characteristic photoparoxysmal response on electroencephalogram provided an important clue for the correct diagnosis of late infantile neuronal ceroid-lipofuscinosis, which was confirmed later with electron microscope examination of a brain biopsy. In patients with rapid neurologic deterioration, diagnosis of neuronal ceroid-lipofuscinosis should be considered and an electroencephalogram should be performed using photic stimulation to look for characteristic findings.