Bahram Mokri

The Monro–Kellie hypothesis Applications in CSF volume depletion

More than two centuries ago, Alexander Monro applied some of the principles of physics to the intracranial contents and for the first time hypothesized that the blood circulating in the cranium was of constant volume at all times. This hypothesis was supported by experiments by Kellie. In its original form, the hypothesis had shortcomings that prompted modification by others. What finally came to be known as the Monro–Kellie doctrine, or hypothesis, is that the sum of volumes of brain, CSF, and intracranial blood is constant. An increase in one should cause a decrease in one or both of the remaining two. This hypothesis has substantial theoretical implications in increased intracranial pressure and in decreased CSF volume. Many of the MRI abnormalities seen in intracranial hypotension or CSF volume depletion can be explained by the Monro–Kellie hypothesis. These abnormalities include meningeal enhancement, subdural fluid collections, engorgement of cerebral venous sinuses, prominence of the spinal epidural venous plexus, and enlargement of the pituitary gland.

Duchenne dystrophy: Electron microscopic findings pointing to a basic or early abnormality in the plasma membrane of the muscle fiber

In seven patients with Duchenne dystrophy, high-resolution phase microscopy demonstrated a population of non-necrotic fibers with one or more focal lesions. The typical lesion was wedge-shaped, with the base resting on the fiber surface. In the electron microscope, the plasma membrane overlying the lesion was either absent or disrupted, while the basement membrane was always preserved. Within the lesion, there were cytoplasmic abnormalities, and in the neighboring fiber region, the myofibrils were usually highly contracted. The structural defect in the plasma membrane suggested that this site was an ineffective cellular barrier. This was confirmed by the frequent ingress of peroxidase-containing extracellular fluid into the lesions. In two control subjects, peroxidase penetration into fibers was seen only rarely and only with other evidence of mechanical injury to the specimen. The findings point to an early and possibly basic abnormality in the plasma membrane of the muscle fiber in Duchennes dystrophy.

Headache and neck pain in spontaneous internal carotid and vertebral artery dissections

We studied the characteristics of headaches in 161 consecutive symptomatic patients with spontaneous dissections of the internal carotid artery (n equals 135) or the vertebral artery (n equals 26).For patients with internal carotid artery dissection (ICAD), the mean age was 47 years and for those with vertebral artery dissection (VAD), 40.7 years. A history of migraine was present in 18% of the ICAD group and in 23% of the VAD group. Headache was reported by 68% of the patients with ICAD and by 69% of those with VAD, and, when present, it was the initial manifestation in 47% of those with ICAD and in 33% of those with VAD. Ten percent of patients with ICAD had eye, facial, or ear pain without headache. The median interval from onset of headache to development of other neurologic manifestations was 4 days for the ICAD group and 14.5 hours for the VAD group. For all dissections, headaches typically were ipsilateral to the side of dissection. In the ICAD group, headaches were limited to the anterior head in 60% of patients and were steady in 73% and pulsating in 25%. In the VAD group, headaches were distributed posteriorly in 83% of patients and were steady in 56% and pulsating in 44%. Neck pain was present in 26% of patients with ICAD (anterolateral) and in 46% of those with VAD (posterior). The median duration of the headache in patients with VAD and ICAD was 72 hours, but headaches became prolonged, persisting for months to years, in four patients with ICAD. NEUROLOGY 1995;45: 1517-1522

Spontaneous dissections of the vertebral arteries.

Clinical and angiographic features and outcome in 25 patients with spontaneous dissections of the vertebral arteries are described. Most patients were in their fourth or fifth decade of life, and women predominated. Forty-eight percent of the patients were hypertensive. Angiographic evidence of fibromuscular dysplasia was noted in one only. Brainstem ischemic symptoms (usually a lateral medullary syndrome) and ipsilateral occipital headache and neck pain (often preceding but sometimes associated with or following the brainstem ischemic event) were the most common clinical findings. The angiographic features in decreasing order of frequency were luminal stenosis (often irregular and tapered), aneurysm, occlusion, and intimal flap. On follow-up, most of the patients (88%) made complete or very good recoveries. Angiographic abnormalities either subsided or improved in 76%. Multivessel dissection (involvement of both vertebral arteries or one or both vertebral arteries and one or both internal carotid arteries) was noted in about two-thirds of the patients. This tendency of vertebral artery dissections to involve multiple cervicocephalic vessels concurrently, if not simultaneously, implies that four-vessel angiography should be attempted if a vertebral artery dissection is visualized. It also raises the possibility of an underlying arteriopathy that predisposes the vessel to dissection.

Incidence and outcome of cervical artery dissection A population-based study

Background: Incidence rates for internal carotid artery dissection (ICAD) have been reported to be 2.6 to 2.9 per 100,000, but reliable epidemiologic data for vertebral artery dissection (VAD) are not available. Objective: To determine the incidence rate of cervical artery dissection (CAD) in a defined population. Methods: With IRB approval, we used the medical record linkage system of the Rochester Epidemiology Project to identify all patients diagnosed with spontaneous ICAD and VAD for the period of 1987–2003 in Olmsted County, MN. Results: Of 48 patients with CAD, there were 32 patients with ICAD and 18 patients with VAD. In Olmsted County, the average annual incidence rate for ICAD was 1.72 per 100,000 population (95% CI, 1.13 to 2.32) and for VAD 0.97 per 100,000 population (95% CI, 0.52 to 1.4). The average annual incidence rate for CAD was 2.6 per 100,000 population (95% CI, 1.86 to 3.33). The most frequently encountered symptoms in CAD were head or neck pain (80%), cerebral ischemia (TIA or infarct) (56%), and Horner syndrome (25%). Good outcome (defined as modified Rankin score of 0 to 2) was seen in 92% of patients. No recurrence of dissection was observed during a mean 7.8 years of follow-up. Conclusions: Internal carotid artery dissection was detected approximately twice as frequently as vertebral artery dissection in the overall study, but in the latter half of the study period, vertebral artery and internal carotid artery dissection incidence rates were equivalent. The majority of cervical artery dissection patients in the community have excellent outcome, and contrary to many tertiary referral series, re-dissection is rare.

Spontaneous Cerebrospinal Fluid Leaks: From Intracranial Hypotension to Cerebrospinal Fluid Hypovolemia—Evolution of a Concept

Intracranial hypotension causes orthostatic headaches and diffuse pachymeningeal gadolinium enhancement on magnetic resonance imaging with or without subdural fluid collections or imaging evidence of descent of the brain. A review of the literature and my experience and investigations in the past decade reveal a broadening clinical and imaging spectrum of the syndrome. Besides the classic clinical-imaging syndrome of orthostatic headaches, diffuse pachymeningeal gadolinium enhancement, and low cerebrospinal fluid (CSF) pressure, several modes of presentation are recognized, including (1) the typical clinical-imaging syndrome with CSF pressures consistently within normal limits, (2) absence of diffuse pachymeningeal gadolinium enhancement with presence of low CSF pressures and typical clinical manifestations, and (3) absence of headaches despite low CSF pressures and presence of diffuse pachymeningeal gadolinium enhancement. Furthermore, in some patients with headaches, the orthostatic headaches may evolve into lingering chronic daily headaches, although they may be more prominent in upright positions. What determines the various clinical and imaging features of this syndrome seems to be the loss of CSF volume as the independent variable, while other manifestations, including clinical features, CSF pressures, and imaging abnormalities, are variables dependent on the CSF volume. The term CSF hypovolemia is proposed for this syndrome because the term intracranial hypotension no longer seems adequate to embrace all the variations that have emerged.

Internal carotid artery dissection in a community. Rochester, Minnesota, 1987-1992.

Background and Purpose Cervical internal carotid artery dissections are diagnosed with an increasing frequency, but reliable epidemiologic data are not available. The aim of this study was to determine the incidence rate of spontaneous cervical internal carotid artery dissection in a defined population. Methods Using the medical record linkage system used for epidemiologic studies in Rochester, Minn, all patients diagnosed with spontaneous cervical ICA dissection for 1987 through 1992 were identified. Results A total of 10 patients with spontaneous cervical internal carotid artery dissection (6 women and 4 men; mean age, 44 years) were identified. For the period 1987 through 1992, the average annual incidence rate for all ages was 2.6 per 100 000 (95% confidence intervals, 0.9 to 4.2). Conclusions This study, for the first time, provides incidence rates for spontaneous cervical internal carotid artery dissections. No diagnoses were made before 1987, probably reflecting an increased awareness of the disorder among physicians. (Stroke. 1993;24:1678-1680.)

Cranial nerve palsy in spontaneous dissection of the extracranial internal carotid artery

Cranial nerve palsy was present in 23 of 190 consecutive adult patients (12%) with spontaneous dissection of the extracranial internal carotid artery.Ten patients (5.2%) had a syndrome of lower cranial nerve palsies (with invariable involvement of cranial nerve XII with or without additional involvement of cranial nerves XI, X, and IX), seven (3.7%) had palsy of cranial nerve V, and five (2.6%) had a syndrome of ocular motor palsies. Palsy of cranial nerve VIII and ischemic optic neuropathy occurred in one patient each. Three patients had dysgeusia without other cranial nerve involvement, presumably due to involvement of the chorda tympani nerve. Headache or face pain (often unilateral) was present in 83% of patients. Other associated manifestations were cerebral ischemic symptoms, bruits, or oculosympathetic palsy. In one patient, cranial nerve palsy was the only manifestation of internal carotid artery dissection, and in another patient, the disease presented only as a palsy of cranial nerve XII and oculosympathetic palsy. In six patients, a syndrome of hemicrania and ipsilateral cranial nerve palsy was the sole manifestation of internal carotid artery dissection. Cranial nerve palsy is not rare in internal carotid artery dissection. Compression or stretching of the nerve by the expanded artery may explain some but not all of the palsies. An alternative mechanism is likely interruption of the nutrient vessels supplying the nerve. NEUROLOGY 1996;46: 356-359

The efficacy of epidural blood patch in spontaneous CSF leaks

Of 25 consecutive patients with spontaneous CSF leaks treated with epidural blood patch (EBP), nine patients (36%) responded well to the first EBP. Of 15 patients who received a second EBP, five became asymptomatic (33%). Of eight patients who received three or more EBP (mean 4), four patients (50%) responded well.

Amphiphysin autoimmunity: paraneoplastic accompaniments

Amphiphysin‐IgG was identified in 71 patients among 120,000 evaluated serologically for paraneoplastic autoantibodies. Clinical information was available for 63 patients. Cancer was detected in 50 (mostly limited), proven histologically in 46, and was imaged intrathoracically in 4 patients (lung, small–cell [27] and non–small cell [1]), breast [16] and melanoma [2]). Neurological accompaniments included (decreasing frequency): neuropathy, encephalopathy, myelopathy, stiff‐man phenomena, and cerebellar syndrome. In a case examined neuropathologically, parenchymal T‐lymphocyte infiltration (predominantly CD8+) was prominent in lower brainstem, spinal cord, and dorsal root ganglion. Coexisting paraneoplastic autoantibodies, identified in 74% of patients, predicted a common neoplasm and indicated other neuronal autoantigen targets that plausibly explained several neurological manifestations; for example, P/Q‐type Ca2+‐channel antibody with Lambert–Eaton syndrome (n = 5), anti‐neuronal nuclear antibody type 1 with sensory neuronopathy (n = 7), K+‐channel antibody with limbic encephalitis (n = 1) or neuromyotonia (n = 1), and collapsin response‐mediator protein‐5‐IgG with optic neuritis (n = 3). Patients with isolated amphiphysin‐IgG (n = 19) were more likely to be women (with breast cancer, p < 0.05) and to have myelopathy or stiff‐man phenomena (p < 0.01). Overall, a minority of women (39%) and men (12%) had stiff‐man phenomena. Only 10% of women (some with lung carcinoma) and 4% of men fulfilled diagnostic criteria for stiff‐man syndrome. Ann Neurol 2005;58:96–107