Neurological complications of venomous snake bites: a review.

Snake bite envenoming is a neglected tropical disease affecting millions of people living in the developing world. According to the offending snake species, the clinical picture may be dominated by swelling and soft tissue necrosis in the bitten limb, or by systemic or neurological manifestations. Serious neurological complications, including stroke and muscle paralysis, are related to the toxic effects of the venom, which contains a complex mixture of toxins affecting the coagulation cascade, the neuromuscular transmission, or both. Metalloproteinases, serine proteases, and C-type lentins (common in viper and colubrid venoms) have anticoagulant or procoagulant activity and may be either agonists or antagonists of platelet aggregation; as a result, ischemic or hemorrhagic strokes may occur. In contrast, the venom of elapids is rich in phospholipase A(2) and three-finger proteins, which are potent neurotoxins affecting the neuromuscular transmission at either presynaptic or post-synaptic levels. Presynaptic-acting neurotoxins (called ß-neurotoxins) inhibit the release of acetylcholine, while post-synaptic-acting neurotoxins (called α-neurotoxins) cause a reversible blockage of acetylcholine receptors. Proper management of the envenomed patient, including prompt transport to the hospital, correction of the hemostatic disorder, ventilatory support, and administration of antivenom, significantly reduces the risk of neurological complications which, in turn, reduce the mortality and improve the functional outcome of survivors.

Frailty and Risk of Falls in Community-Dwelling Older Adults Living in a Rural Setting. The Atahualpa Project.

BACKGROUND: Data supporting a link between frailty and risk of falls is mostly confined to individuals living in urban centers, where risk factors and lifestyles are different from that of rural settings. OBJECTIVE: To assess the association between frailty and risk of falls in older adults living in rural Ecuador. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Community-dwellers aged ≥60 years living in a rural Ecuadorian village, in whom frail status and risk of falls were assessed. MEASUREMENTS: Frailty was evaluated by the Edmonton Frailty Scale (EFS) and risk of falls by the Downton Fall Risk Index (DFRI). Multivariate models were fitted to evaluate whether frailty was associated with risk of falls (dependent variable), after adjusting for demographics, alcohol intake, cardiovascular risk factors, sleep quality, symptoms of depression, and history of an overt stroke. Correlation coefficients were constructed to assess confounders modifying this association. RESULTS: A total of 324 participants (mean age: 70.5±8 years) were included. The mean EFS score was 4.4±2.5 points, with 180 (56%) participants classified as robust, 76 (23%) as pre-frail and 68 (21%) as frail. The DFRI was positive in 87 (27%) participants. In univariate analysis, the EFS score was higher among participants with a positive DFRI (p<0.001). The number of frail individuals was higher (p<0.001), while that of robust individuals was lower (p<0.001) among those with a positive DFRI. Adjusted logistic regression models showed no association between frailty and the DFRI. Correlation coefficients showed that age, high glucose levels, and history of an overt stroke tempered the association between frailty and the risk of falls found in univariate analyses. CONCLUSIONS: Frailty is not independently associated with risk of falls in older adults living in a remote rural setting. Further studies are needed to assess the impact of frailty on the risk of falls in these populations.

Revised diagnostic criteria for neurocysticercosis.

BACKGROUND: A unified set of criteria for neurocysticercosis (NCC) has helped to standardize its diagnosis in different settings. METHODS: Cysticercosis experts were convened to update current diagnostic criteria for NCC according to two principles: neuroimaging studies are essential for diagnosis, and all other information provides indirect evidence favoring the diagnosis. Recent diagnostic advances were incorporated to this revised set. RESULTS: This revised set is structured in absolute, neuroimaging and clinical/exposure criteria. Absolute criteria include: histological confirmation of parasites, evidence of subretinal cysts, and demonstration of the scolex within a cyst. Neuroimaging criteria are categorized as major (cystic lesions without scolex, enhancing lesions, multilobulated cysts, and calcifications), confirmative (resolution of cysts after cysticidal drug therapy, spontaneous resolution of single enhancing lesions, and migrating ventricular cysts on sequential neuroimaging studies) and minor (hydrocephalus and leptomeningeal enhancement). Clinical/exposure criteria include: detection of anticysticercal antibodies or cysticercal antigens by well-standardized tests, systemic cysticercosis, evidence of a household Taenia carrier, suggestive clinical manifestations, and residency in endemic areas. Besides patients having absolute criteria, definitive diagnosis can be made in those having two major neuroimaging criteria (or one major plus one confirmative criteria) plus exposure. For patients presenting with one major and one minor neuroimaging criteria plus exposure, definitive diagnosis of NCC requires the exclusion of confounding pathologies. Probable diagnosis is reserved for individuals presenting with one neuroimaging criteria plus strong evidence of exposure. CONCLUSIONS: This revised set of diagnostic criteria provides simpler definitions and may facilitate its more uniform and widespread applicability in different scenarios.

Sex-related severity of inflammation in parenchymal brain cysticercosis.

To determine sex-related differences in the severity of host inflammatory reaction to cysticercosis, we studied computed tomographic findings in 100 patients with parenchymal neurocysticercosis and cerebrospinal fluid results in 239 patients with subarachnoid neurocysticercosis. Computed tomographic and cerebrospinal fluid data in male subjects were compared with those obtained in female subjects. We found that when cysticerci are found in brain parenchyma, women develop a greater degree of inflammation; such differences disappear when cysticerci are found in the subarachnoid space. Our results point out the possibility of a factor located within brain parenchyma that accounts for the observed sex-related differences in the severity of immune response to the parasite; this factor could also play a role in the pathogenesis of other immunologically mediated diseases of the brain that may occur more frequently in women. To our knowledge, this study is the first in demonstrating that sex is a risk factor for the severity of inflammatory response within brain parenchyma to a parasitic disease.

Lacunar syndrome due to neurocysticercosis.

Seven patients with neurocysticercosis presented with a lacunar syndrome. Four patients had sensorimotor stroke, two had pure motor hemiparesis, and one had ataxic hemiparesis. In every patient, computed tomography or magnetic resonance imaging or both showed a lacunar infarct that was secondary to the occlusion of a terminal vessel affected by endarteritis and was most commonly associated with cysticerci in the suprasellar cistern. Diagnosis of neurocysticercosis was difficult on clinical grounds, but proper integration of data from computed tomography and cerebrospinal fluid analysis provided an accurate diagnosis in every case. Neurocysticercosis should be considered in the differential diagnosis of young adults with a lacunar syndrome who come from areas of the world where this disease is endemic.

Short course of albendazole therapy for neurocysticercosis.

Albendazole is now used for therapy of neurocysticercosis; however, duration of treatment has usually been empirically determined. In this study we shortened the length of therapy from one month in previous reports, to one week. Twelve patients with parenchymal brain cysticercosis were treated with albendazole for eight days at daily doses of 15 mg/kg of body weight. After three months of treatment the number of cysts on computed tomography had decreased from 185 to six; a 97% reduction in the number of lesions. Total remission of all cysts was seen in nine patients. Two cases had been unsuccessfully treated before with praziquantel, in both instances albendazole therapy was effective with 100% improvement. Our results indicated that a short course of albendazole is highly effective for treatment of neurocysticercosis.

Brain-stem tuberculoma. An analysis of 11 patients.

The clinical and radiologic findings in 11 patients with brain-stem tuberculoma were reviewed. Clinical manifestations included various combinations of focal signs and symptoms of subacute onset, similar to those produced by other space-occupying lesions of the brain stem. Evidence of systemic tuberculosis was found in six cases (55%). Computed tomography (CT) usually showed an isodense or hyperdense brain-stem mass with abnormal contrast enhancement; associated supratentorial granulomas were found in four cases, and hydrocephalus was found in two cases. Magnetic resonance imaging showed irregular brain-stem lesions with long T1 and short T2 relaxation times. Cerebrospinal fluid findings were also nonspecific, as smears for acid-fast bacilli were most often negative. An incorrect diagnosis of pontine glioma was made in one patient. In contrast, proper integration of data from CT and magnetic resonance imaging findings, cerebrospinal fluid analysis, and x-ray films of the chest permitted an accurate diagnosis in ten cases. Prompt therapy with antituberculous drugs resulted in clinical improvement, documented by CT, in most patients. Brain-stem tuberculoma should be suspected in patients with space-occupying lesions of the brain stem who live in geographic areas where tuberculosis is endemic. Early diagnosis and prompt medical therapy are important in preventing mortality and reducing morbidity.

Albendazole therapy for giant subarachnoid cysticerci.

Albendazole is considered to be the drug of choice for treatment of parenchymal brain cysticercosis. Its efficacy, however, for treatment of subarachnoid cysticerci has not been established, to our knowledge. In this study, we treated four patients who had giant subarachnoid cysticerci with albendazole at daily doses of 15 mg/kg of body weight for 8 days. Computed tomographic studies showed that all cysts disappeared 3 months after the end of treatment. This was associated with marked clinical improvement in every case. Our results indicated that albendazole is highly effective for treatment of this form of the disease.

Neurocysticercosis among patients with cerebral gliomas.

BACKGROUND: Parasites have been implicated in the pathogenesis of human cancer. Anecdotal reports have suggested an association between neurocysticercosis and brain tumors. OBJECTIVE: To determine whether neurocysticercosis is a risk factor for cerebral glioma. DESIGN: Case-control study. SETTING: A university general hospital and a cancer referral center. PATIENTS: Forty-three consecutive patients with a cerebral glioma and 172 controls matched for age, sex, and socioeconomic status. METHODS: We determined the ratio between the frequency of neurocysticercosis in patients with a cerebral glioma and in matched controls. We also evaluated differences in the characteristics of the patients and in the histological type of the neoplasm among case patients with and without neurocysticercosis. In addition, we noted relationships between the location of the cerebral glioma and that of parasitic lesions. RESULTS: Eight (16.8%) of 43 patients with a glioma and 5 (2.9%) of 172 controls had neurocysticercosis (P < .001). The odds ratio for this association was 7.63 (95% confidence interval, 2.03-31.09). Patients with glioma and neurocysticercosis were older than those without neurocysticercosis (mean [+/-SD] age, 62.75 +/- 18.34 years vs 44.69 +/- 14.04 years; P = .02). Glioblastoma multiforme was more frequent among case patients with neurocysticercosis than among those without neurocysticercosis (87.5% vs 48.6%); however, this difference was not statistically significant (P = .24). Six of the 8 patients with neurocysticercosis and a cerebral glioma had calcified parasitic lesions within and around the tumor. CONCLUSIONS: Results from this study suggest that neurocysticercosis is a risk factor for cerebral glioma. The intense astrocytic gliosis that surrounds calcified cysticerci, together with the suppression of the cellular immune response induced by cysticerci, may contribute to the development of malignant glial cells in patients with neurocysticercosis.

Prognostic factors for seizure recurrence after withdrawal of antiepileptic drugs in patients with neurocysticercosis.

We tapered antiepileptic drugs in 40 patients with epilepsy due to neurocysticercosis who had been free of seizures for 2 years. All patients previously received a course of albendazole that resulted in complete destruction of brain cysts. We followed the patients prospectively from the time of diagnosis until 12 months after antiepileptic drug withdrawal. We evaluated the following prognostic factors for seizure recurrence: sex, number of seizures before control, type of seizures, number of parenchymal brain cysts before albendazole therapy, EEG findings, and CT findings after albendazole therapy. In the univariate analysis of prognostic factors for seizure recurrence, the development of brain calcifications caused by albendazole was the only factor associated with a significantly higher rate of relapse (p = 0.004). The multivariate analysis showed that patients who had both recurrent seizures and multiple brain cysts also had a higher risk of relapse than those with single seizures or single cysts (p = 0.05). This study suggests that the prognosis of epilepsy due to neurocysticercosis is not as benign as previously thought. Patients with residual calcifications and those with both recurrent seizures and multiple cysts before albendazole therapy have the highest rate of relapse after withdrawal of antiepileptic drugs.

Heavy nonencephalitic cerebral cysticercosis in tapeworm carriers. The Cysticercosis Working Group in Perú.

We describe 11 patients with massive brain infection with viable cysticerci, undetectable inflammatory reaction on CNS imaging, and an unexpectedly high (82%) prevalence of tapeworm infection. With the exception of two individuals with heavy parasite loads, patients had a relatively benign clinical course and tolerated the use of cysticidal drugs. This group of patients represents a particular presentation of neurocysticercosis, different from the previously described syndromes of cysticercotic encephalitis and disseminated systemic cysticercosis.

Single-day praziquantel versus 1-week albendazole for neurocysticercosis.

The efficacy of albendazole (15 mg/kg/d for 1 week) was compared with praziquantel (100 mg/kg in three divided doses at 2-hour intervals) for therapy of parenchymal brain cysticercosis. Ten patients were treated with albendazole and 10 patients with praziquantel. Although the total number of cysts was significantly reduced from 64 to 7 in patients treated with albendazole and from 59 to 24 in those treated with praziquantel, the number of patients improving with albendazole was not significantly different from those treated with praziquantel.

Epilepsy due to neurocysticercosis: analysis of 203 patients.

We reviewed clinical, EEG, and CT findings of 203 patients with epilepsy due to neurocysticercosis. Seizures were generalized in 121 patients and partial in 82. Thirty-two patients had focal signs and eight had papilledema. Eighty-one had generalized and 16 had focal EEG abnormalities. CT showed parenchymal brain calcifications in 53 patients and cysts in 150. There was an increased rate of focal signs in patients with single cysts as compared with patients with multiple cysts, and focal EEG abnormalities were present only in patients with single cysts. Fifty patients were lost to follow-up. The remaining 153 patients were followed for 28 +/- 6 months; of these, 31 had calcifications and 122 had cysts. Anticonvulsants were started after the first visit in every patient. The 31 patients with calcifications remained free of seizures. Ninety-five of the 122 patients with cysts were also treated with anticysticercal drugs; of these, 79 (83%) had control of seizures. In contrast, only seven (26%) of 27 patients who did not receive anticysticercal drugs had control of seizures, indicating a strong correlation between the use of anticysticercal drugs and seizure control. Finally, of the 21 patients in whom anticonvulsants were withdrawn, 16 had relapses.

Proposed diagnostic criteria for neurocysticercosis.

Neurocysticercosis is the most common helminthic infection of the CNS but its diagnosis remains difficult. Clinical manifestations are nonspecific, most neuroimaging findings are not pathognomonic, and some serologic tests have low sensitivity and specificity. The authors provide diagnostic criteria for neurocysticercosis based on objective clinical, imaging, immunologic, and epidemiologic data. These include four categories of criteria stratified on the basis of their diagnostic strength, including the following: 1) absolute--histologic demonstration of the parasite from biopsy of a brain or spinal cord lesion, cystic lesions showing the scolex on CT or MRI, and direct visualization of subretinal parasites by funduscopic examination; 2) major--lesions highly suggestive of neurocysticercosis on neuroimaging studies, positive serum enzyme-linked immunoelectrotransfer blot for the detection of anticysticercal antibodies, resolution of intracranial cystic lesions after therapy with albendazole or praziquantel, and spontaneous resolution of small single enhancing lesions; 3) minor--lesions compatible with neurocysticercosis on neuroimaging studies, clinical manifestations suggestive of neurocysticercosis, positive CSF enzyme-linked immunosorbent assay for detection of anticysticercal antibodies or cysticercal antigens, and cysticercosis outside the CNS; and 4) epidemiologic--evidence of a household contact with Taenia solium infection, individuals coming from or living in an area where cysticercosis is endemic, and history of frequent travel to disease-endemic areas. Interpretation of these criteria permits two degrees of diagnostic certainty: 1) definitive diagnosis, in patients who have one absolute criterion or in those who have two major plus one minor and one epidemiologic criterion; and 2) probable diagnosis, in patients who have one major plus two minor criteria, in those who have one major plus one minor and one epidemiologic criterion, and in those who have three minor plus one epidemiologic criterion.

Taenia solium cysticercosis.

Cysticercosis, the infection of the larval tissue stage of the pork tapeworm, Taenia solium, is endemic to most developing countries and increasingly is seen in industrialized countries because of immigration. Human infection is a major cause of acquired epilepsy, and porcine infection causes important economic losses to farm workers. Clinical manifestations vary because of the variable number, size, and location of the cysts and the immune response of the host. Diagnosis is based on imaging techniques (CT and MR imaging) and serology (immunoblot). Current research efforts are centered on control and eradication of the taeniasis cysticercosis complex in endemic areas.

Comparison of therapeutic regimen of anticysticercal drugs for parenchymal brain cysticercosis.

The efficacy of different regimens of therapy for parenchymal brain cysticercosis either with praziquantel (PZQ) or with albendazole (ALB) was compared in 114 patients. Four schemes of treatment were used: PZQ 50 mg/kg per day for 15 days, PZQ 50 mg/kg per day for 8 days, ALB 15 mg/kg per day for 30 days, and ALB 15 mg/kg per day for 8 days. Three months after therapy, it was apparent that both PZQ and ALB were effective, as shown by the disappearance of cystic lesions in computed tomographic scans. Thirty-three control patients followed for a mean of 11 months had no spontaneous remission of lesions. When comparing PZQ with ALB, the latter was found to be more effective than the former for both the full and the short course of treatment: 85% vs 60% and 85% vs 48% disappearance of lesions, respectively (P less than 0.001). Comparison of the full vs the short course of PZQ showed that the short course had a further 12% reduction in drug effectiveness. In contrast, the length of ALB therapy could be shortened without lessening its efficacy. Based on these results, an 8-day course of ALB is recommended as treatment for parenchymal brain cysticercosis; a 15-day course of PZQ could be subsequently used in those patients who show only partial response to ALB.

Proposal of diagnostic criteria for human cysticercosis and neurocysticercosis.

Taenia solium cysticercosis is a major public health problem in several areas of the world. While the disease has a recognized etiologic agent, its definitive histological diagnosis is not possible in most cases because this parasite tends to lodge in cerebral tissues where routine biopsy is not feasible. Therefore, the diagnosis of human cysticercosis (and neurocysticercosis) should rest on the proper interpretation of the patients' symptoms together with data provided by radiological studies and immunologic tests for the detection of anticysticercal antibodies. Unfortunately, the pleomorphism of this parasitic disease creates confusion when non-specific clinical, radiological, or immunologic criteria alone are used to detect cases among populations or to diagnose hospitalized patients with neurological manifestations. We propose a chart of diagnostic criteria for human cysticercosis that objectively permit clinicians and health care workers to evaluate clinical, radiological, immunologic, and epidemiologic data of patients. The chart uses four degrees of criteria: absolute, major, minor, and epidemiologic, that were selected on the basis of their individual diagnostic strength. Interpretation of such criteria will result in three categories of diagnostic certainty: definitive, probable and possible, according to the likelihood that cysticercosis is present in a given person.