Myelopathy but normal MRI: where next?

For most patients presenting with a spinal cord syndrome MR scanning has become the key investigation in establishing the diagnosis. However, myelopathy with normal spinal imaging remains a common clinical conundrum. In this review we discuss the diagnoses to consider for the neurologist presented with a patient with "MR normal myelopathy". We will illustrate this scenario with a series of short cases and consider the further investigation of "MRI normal" myelopathy.

Overdiagnosis of TIA and minor stroke: experience at a regional neurovascular clinic.

We compared the referral diagnoses of TIAs and minor strokes made by non-specialists with those of two consultant neurologists, in 565 consecutive cerebrovascular clinic patients, of whom 508 (90%) were referred with a diagnosis of any TIA or stroke. In 373 (73%), the neurologists felt the diagnosis of a cerebrovascular event to be correct. Agreement with the vascular syndrome (CVA vs. TIA) was significantly higher for patients with a referral diagnosis of stroke (136/176) (77%) than it was for patients with a referral diagnosis of TIA (200/332) (60%) (difference in proportions 17%, 95% CI 9-25). In 37 patients (7%) the neurologists confirmed the diagnosis of cerebrovascular disease but not the specific TIA/stroke diagnosis. Vascular surgeons were more likely to be correct in their referral diagnosis of carotid territory cerebrovascular disease (88% correct) than all other sources combined (63% correct) (difference in proportions 25%, 95% CI 11-39), but there was no significant variation in diagnostic accuracy between other individual groups. In 135/508 patients (27%) referred as any TIA or stroke, the diagnosis of cerebrovascular disease was undone. Alternative diagnoses included migraine (3%), epilepsy (1%), hyperventilation (1%), multiple sclerosis (1%) and a case of idiopathic Parkinson's disease, but many symptoms (8%) were unclassifiable. A strict comparison of diagnostic accuracy would have required assessment of patients not referred for specialist opinion, to estimate false-negative as well as false-positive diagnoses. However, in this patient group (which reflects current local practice) TIAs and strokes seem overdiagnosed.

Pathological heterogeneity of clinically diagnosed corticobasal degeneration.

Two patients fulfilling suggested clinical diagnostic criteria for corticobasal degeneration (CBD) are presented, who were found at postmortem to have alternative pathological diagnoses not suspected during life, namely, Alzheimer's disease and Pick's disease, respectively. The nosological position of these cases is considered in light of a literature review of previous reports of clinically diagnosed corticobasal degeneration with atypical (not corticobasal degeneration) pathology. Since such phenocopies may be common, we suggest that all clinically diagnosed cases of corticobasal degeneration should initially be labelled as "corticobasal degeneration syndrome" (CBDS) to emphasize that this is a diagnosis based on clinical phenotype, with the term corticobasal degeneration being reserved for the specific neuropathological phenotype, which itself may have a variety of clinical presentations.

Positive serological tests for syphilis and administration of intravenous immunoglobulin.

We report the case of a man who tested positive for syphilis following the intravenous administration of human normal immunoglobulin as part of the treatment of Guillain-Barré syndrome. The chronology of the testing suggested the passive acquisition of treponemal antibody. This phenomenon is not widely documented in the medical literature, but is a theoretical risk of treatment, and serves as a reminder to be cautious in the interpretation of such serological tests.

Neurological presentation of intravascular lymphoma: report of two cases and discussion of diagnostic challenges.

About a third of patients with intravascular lymphoma (IVL) present to the neurologist with symptoms mimicking thromboembolic events. Diagnosis is difficult, and often made postmortem. As remission may be induced in almost half of patients with combination chemotherapy, early diagnosis of this rare disease is essential. We report two cases of IVL. A 62-year-old male presented with hyperacute myelopathy followed by cortical ischaemic events. The diagnosis was reached with frontal cortical and meningeal biopsy. A 56-year-old female had symptoms of transient ischaemic events, subacute dementia, weight loss and fever. As the disease progressed, she developed nephrotic syndrome and thrombocytopenia. Diagnosis was made postmortem. Our cases illustrate that IVL should be considered in the differential diagnosis of cerebral and systemic vasculitis and subacute bacterial endocarditis. Literature suggests IVL can also mimic Creutzfeld-Jakob disease and paraneoplastic encephalomyelitis.

Spinally projecting neurons in the dorsal column nuclei: distribution, dendritic trees and axonal projections. A retrograde HRP study in the cat.

The distribution, dendritic trees and axonal courses of spinally projecting cells in the dorsal column nuclei were studied after labelling by retrograde HRP transport. The region of densest distribution was at the base of the two nuclei and in the area between them, extending for about 2 mm caudally from the obex. Only very few cells were found inside the cell cluster regions of the nuclei, where their dendrites had a free stellate form. The great majority, lying between, deep, or rostral to the cluster regions, also had a stellate form, except where they impinged on the boundaries of the cluster regions or on other nuclear borders; the spread of dendrites was dramatically restricted at such boundaries, often leading to a fusiform appearance in transverse sections which however was not evident in the parasagittal plane. No justification was therefore found for subdividing the population on morphological grounds. Axons of these cells descended ipsilaterally in either the medial part of the dorsolateral fascicle or in the adjacent lateral part of the cuneate fascicle, at cervical levels, and probably in about equal numbers. Most axons destined for the DLF followed a deep caudolateral trajectory, while many destined for the DC had a more dorsal or lateral course. Collateral branches were seen within the nuclei but could not be followed far. The fact that few if any cells lying in the region of maximum distribution of the spinally projecting cells were labelled following injections of HRP into the thalamic ventroposterior nucleus emphasizes that they form a distinctive entity within this medullary nuclear complex, and that any axon branches they give into the contralateral brainstem must have some other destination than the VPL. Two other groups of neurons were labelled by HRP implants into the dorsal columns - one in the ventrolateral medullary reticular formation, and the other in the nucleus of the solitary tract.

Cerebral venous thrombosis.

Cerebral venous thrombosis is a treatable and under-recognised cause of a benign intracranial hypertension syndrome, and may also cause focal signs, seizures, and depression of consciousness.

Postsynaptic dorsal column neurons in the cat: a study with retrograde transport of horseradish peroxidase.

The numbers, laminar position, perikaryal and dendritic morphology, and axonal trajectories of postsynaptic cells ascending the dorsal column have been studied after implantation of HRP pellets in either the dorsal columns or dorsal column nuclei after destruction of the dorsolateral fascicle on one side. Observations made throughout the spinal cord gave estimated figures of 800-1000 and 1700-2000 cells in lumbosarcal and brachial enlargements respectively on the side of the implant. The commonest type (C), centred on lamina IV, had dendritic trees greatly extended rostrocaudally and restricted mediolaterally in the lateral dorsal horn, the extension and restriction diminishing for more medial cells. Type B cells differed dramatically, with large straight dendrites in the transverse plane and large perikarya in medial lamina V. Type A cells, distinguished by both rostrocaudal and mediolateral restriction in dendritic trees, were only found medially in laminae III and IV. Outside the enlargements, in high lumbar and thoracic cord, many fewer cells were found, corresponding to Type C but with dendrites much elongated rostrocaudally and little mediolateral variation. Many small fusiform cells were found in medial lamina VI in the upper cervical cord, distinct from any of the above. A few cells were found in the cord enlargements in lamina VII of the contralateral ventral horn, with axons crossing through the ventral commissure. The axons of all cell types were tortuous, and some entered the dorsolateral fascicle before crossing into the dorsal column: collaterals were often seen but could not be followed far. A complementary study of cells with axons ascending in the dorsolateral fascicle is reported in the following paper.

Spinocervical neurons and dorsal horn neurons projecting to the dorsal column nuclei through the dorsolateral fascicle: a retrograde HRP study in the cat.

Spinocervical cells were identified by retrograde labelling from implants of HRP in the dorsolateral fascicle after destruction of the dorsal columns. They lay in laminae III and IV throughout the cord in estimated numbers of 700, 450 and 1100 in lumbosacral enlargement, upper lumbar and thoracic cord, and brachial enlargement respectively. In the cord enlargements dendritic trees were mainly or exclusively developed dorsally, with rostrocaudal exceeding mediolateral spread, and a gradient across the dorsal horn, lateral cells showing this contrast most strongly. Dendritic spread was limited at the II/III laminar boundary. Transition occurred at the edge of the enlargements to a shape with extreme rostrocaudal elongation of perikarya and of dendritic trees in upper lumbar and thoracic segments. Axons of spinocervical cells ascended in the most dorsal part of the fascicle, distinguishable from the larger spinocerebellar bundle lying adjacent and ventral. The initial axonal course was tortuous, with local collateral branching, the axon sometimes travelling briefly in the dorsal column. In other experiments implants were made ipsilaterally in the dorsal column nuclei after destruction of the dorsal columns. Cells were few and relatively poorly labelled, for which the reasons are discussed. Some such cells, lying in lamina IV, were similar to spinocervical tract cells and may have projected to both lateral cervical and dorsal column nuclei. Others, at the extreme lateral edge of the mid-dorsal horn, were quite different, with dendrites greatly extended rostrocaudally and primary and higher order dendrites projecting ventrally from the perikaryon.

Cerebral venous thrombosis: new causes for an old syndrome?

The range of disorders affecting the cerebral veins and sinuses is increasing and now includes blood disorders, abnormalities in the patterns of blood flow, and infiltrative or inflammatory conditions, all of which may promote thrombosis. We describe 10 patients with cerebral venous thrombosis: two had protein S deficiency, one had protein C deficiency, one was in early pregnancy, and there was a single case of each of the following: dural arteriovenous malformation, intracerebral arteriovenous malformation, bilateral glomus tumours, systemic lupus erythematosus, Wegener's granulomatosis, non-Hodgkin's lymphoma. The recognition of such diverse aetiology may be importance since clinical features are non-specific, and may consist only of raised intracranial pressure, allowing confusion with 'benign intracranial hypertension'. The existence of effective treatment both for the thrombosis and for many of the underlying disorders makes early diagnosis essential. The prognosis of treated patients may be favourable.

The use of retrograde transport of horseradish peroxidase for studying the dendritic trees and axonal courses of particular groups of tract cells in the spinal cord.

Modifications have been made in Mesulam 's method for labelling neurons by retrograde transport of horseradish peroxidase, with tetramethylbenzidine as chromogen, with the object of increasing the extent of labelling of dendrites and axons. A procedure was devised specifically for studying spinomedullary and medullospinal tract systems, involving implanting easily-made HRP-agar pellets into areas of controlled damage in particular spinal fascicles, and sealing the site of implant with cyanoacrylate glue. Lesions of other fascicles were often made to limit transport to the implanted fascicle. Fourth-order dendrites were regularly labelled over long (30 cm or more) transport distances: axons were also labelled over this whole distance, often allowing exact study of the initial course of particular axons. Controls in both cat and rat showed that the uptake of HRP under these circumstances occurred almost wholly from the region of axonal damage at the site of implant which can be characterized histologically.

Causes of ischaemic stroke in the young.

The causes of ischaemic stroke in young adults are many and diverse. Such patients usually require more extensive investigations in order to find an underlying cause than more elderly patients. It is important that a comprehensive search is made since many of the underlying disorders are treatable. Principal causes are extracranial arterial dissection, cardioembolism, premature atherosclerosis, haematological and immunological disorders and migraine. Drug abuse is becoming increasingly important but the risk of stroke in pregnancy remains unclear. Isolated angiitis of the central nervous system, heritable disorders of connective tissue and other genetically determined disorders (mitochondrial cytopathies, CA-DASIL) account for a small proportion of ischaemic strokes in the young. Management is probably best undertaken by a physician with a specialist interest and, if full investigation fails to elucidate a definite cause, the risk of future stoke is low.

Autosomal dominant cerebellar ataxia with pigmentary macular dystrophy. A clinical and genetic study of eight families.

We describe 54 members of eight families with a distinct autosomal dominant cerebellar ataxia associated with visual failure secondary to a pigmentary macular dystrophy. The presenting symptom was ataxia in two-thirds of patients and visual failure or both in the remainder. The macular abnormalities were often subtle in early cases, even in some with moderately reduced visual acuity. Other neurological features included pyramidal tract signs and a supranuclear ophthalmoplegia with progressive saccadic palsy. Ages of onset and clinical course were very variable, even within families, and included a rapidly progressive, infantile-onset phenotype. Pedigree analysis showed the existence of non-manifesting obligate carriers and anticipation in the offspring of affected fathers; transmission of the disease to severe, infantile-onset cases was always from an affected father. Similar genetic phenomena have been reported in myotonic dystrophy and Huntington's disease and it is likely that the gene mutation in this condition will similarly consist of an unstable trinucleotide repeat expansion.