Alcoholic myelopathy without substantial liver disease. A syndrome of progressive dorsal and lateral column dysfunction.

Five well-nourished, alcoholic patients had a progressive myelopathy. Symptoms began with paresthesias of the feet and progressed to a spastic paraparesis with clinical signs of both lateral and dorsal column involvement. Abstinence from alcohol halted progression but did not cause improvement in the myelopathy. The absence of portacaval shunting or notable liver dysfunction in these patients suggests that a direct toxic effect of alcohol must be considered a possible mechanism of spinal cord damage.

White-centered retinal hemorrhages: a sign of intracranial hemorrhage.

White-centered retinal hemorrhages (so-called "Roth spots") were seen in an 11-year-old girl with spontaneous intraventricular and subarachnoid hemorrhage from a ruptured "berry" aneurysm without underlying systemic disorder.

Man-in-the-barrel syndrome.

In a prospective study of 34 comatose patients who had an episode of systemic hypotension, 11 had the "man-in-the-barrel" syndrome (MIB). They moved both legs spontaneously or in response to pain, but did not move either arm. One of 11 patients (9%) with MIB survived to leave the hospital; 8 of the 23 patients (35%) without MIB recovered. Of patients who moved at least one limb to pain and had intact pupillary, corneal, and oculocephalic reflexes 24 hours after insult, one of nine (11%) patients with MIB survived, compared with six of nine patients (67%) without MIB. MIB is common after cerebral hypoperfusion and carries a poor prognosis.

Delayed postischemic hypoperfusion: a potentially damaging consequence of stroke.

Cerebral blood flow (CBF) was assessed with radioactive butanol and antipyrine during and after 1 hour of unilateral carotid artery occlusion in gerbils. Animals with clinical evidence of stroke demonstrated a marked fall in ipsilateral CBF during occlusion "no-reflow" phenomenon did not develop; instead, blood flow returned to normal 5 minutes after the termination of carotid occlusion. Flow subsequently fell to half the control value, however, and remained depressed for several hours despite local metabolic demands. This delayed imbalance in energy supply and demand creates a potential for additional brain damage that might be prevented by appropriate therapeutic intervention.

Comparison of radio-labeled butanol and iodoantipyrine as cerebral blood flow markers.

Cerebral blood flow (CBF) techniques based on the principle of indicator fractionation rely upon free diffusibility of the blood flow indicator into brain (i.e. complete cerebral extraction). Extraction of two commonly-used indicators, iodoantipyrine and n-butanol, was evaluated in rats by measuring torcular venous efflux after systemic injection of the indicator under conditions of normal and high CBF. The extraction of n-butanol was found to be virtually complete at all blood flows examined; iodoantipyrine, on the other hand, was completely extracted only at flows under 180 ml/100 g/min, despite the fact that the oil: water partition coefficient for iodoantipyrine exceeds that for n-butanol. Brain uptake indices for the two indicators were also measured: brain uptake of n-butanol was greater than that of iodoantipyrine, and the difference was more marked if the indicator entered brain mixed with blood than if it entered as a bloodless bolus. Blood components may thus interact with iodoantipyrine to retard its movement across the blood-brain barrier and thereby limit extraction of this lipid-soluble substance. Inasmuch as iodoantipyrine is diffusion-limited at blood flows above 180 ml/100 g/min, butanol is a more accurate CBF indicator above the normal flow range in the rat.

Regional brain blood flow in the conscious gerbil.

Regional brain blood flow was determined in 23 awake, unparalyzed gerbils with a simplified indicator-fractionation technique. The use of intravenous 14C-butanol, an indicator that is freely diffusible into the brain, eliminated the need for repetitive sampling of arterial and cerebral venous blood and reduced the period of indicator circulation of 10 seconds. Gerbils spontaneously breathing room air (PaCO2 = 32 +/- 1 (SE) mm Hg) had blood flows in whole cerebrum, cerebellum, and brainstem of 102 +/- 4, 93 +/- 5, and 114 +/- 6 ml/100 gm/min respectively. Cerebral blood flow increased linearly with elevations in PaCO2 (r=0.969) and averaged 3.14 +/- 0.17 ml/100gm/min per mm Hg increase in PaCO2. Interpolated cerebral blood flow at a PaCO2 of 40 mm Hg was 127 +/- 2 ml/100 gm/min. This technique is easy and convenient to use, involves no intracranial surgery, requires steady state conditions for only 10 seconds, and minimizes blood loss in small animals. In more discrete brain regions a less volatile indicator is needed.

Risk of recurrent stroke in patients with atrial fibrillation and non-valvular heart disease.

One-hundred-forty patients with atrial fibrillation (AF) due to non-rheumatic, non-valvular heart disease (NVHD) who suffered a cerebral infarct were identified. Fifty-three (38%) died of the initial stroke. The surviving patients were followed up to 9 years without anticoagulant therapy. In the 59 patients available for follow-up, the risk of recurrent cerebral ischemia remained at approximately 20% per year throughout the 9 year observation period. The recurrence rate was the same regardless of age, sex, previous myocardial infarction, or whether chronic AF or intermittent AF were present. Only 7 (12%) died from a second stroke, however. The high annual rate of recurrence and lack of controlled therapeutic trials in this population of patients warrant a prospective study to define the benefits and relative risks of anticoagulant therapy in AF due to NVHD.

Simultaneous measurement of cerebral blood flow and unidirectional movement of substances across the blood-brain barrier: theory, method, and application to leucine.

The uptake of compounds by the brain depends upon cerebral blood flow. To determine the normal blood flow-cerebral extraction relationship, a method for rapid, simultaneous measurement of cerebral blood flow and brain extraction was developed and applied to blood-brain leucine transfer. Awake rats were injected intravenously with a mixture of n-[(14)C]butanol and [(3)H]leucine. The quantities of indicators accumulated over the following 5-12 s in brain and in a sample of arterial blood withdrawn at a know rate were used to determine the flux of butanol and leucine into brain. Butanol extraction was assessed independently by measuring arterial and cerebral venous concentrations of the indicator after a bolus injection. Cerebral blood flow was equal to the ratio of butanol flux into brain to butanol extraction by brain; leucine extraction was then calculated as the ratio of leucine influx to cerebral blood flow. Leucine extraction by brain and cerebral blood flow were shown to be related exponentially. The maximum velocity of active leucine transport was virtually the same at flows of 150 and 400 ml/100 g/min. The present method is theoretically applicable to the measurement of the extraction of any compound from blood by brain. By measuring the normal blood flow-extraction relationship, one can differentiate changes in extraction secondary to altered flow from changes intrinsic to pathologic conditions with inconstant cerebral blood flow.

Early changes in blood brain barrier permeability to small molecules after transient cerebral ischemia.

Brain unidirectional extraction and flux of leucine were measured simultaneously with cerebral blood flow (CBF) at various times after transient global cerebral ischemia in the rat. The results permit an evaluation of blood-brain barrier permeability in the postischemic period independent of alterations in CBF at the time of measurement. Leucine extraction was higher (p less than 0.001) than that of CBF-matched controls at 15 min and 6 hr after 30 min of global cerebral ischemia, but was not different from control at 30 min and 1 h after ischemia. Leucine flux into brain was increased only at 15 min after reperfusion of the brain. Cerebral edema occurs 15-30 min after reperfusion in this ischemia model, but the permeability of the blood-brain barrier to large molecules is unaltered during this period (Petito et al: J Neuropath Exp Neurol 41:423-436, 1982). Increased barrier permeability to small molecules such as leucine may contribute to the production of this early postischemic edema.