Juan Carlos Garcia-Monco

Effect of focal cerebellar lesions on procedural learning in the serial reaction time task

Abstract Prior studies have shown that procedural learning is severely impaired in patients with diffuse cerebellar damage (cortical degeneration) as measured by the serial reaction time task (SRTT). We hypothesize that focal cerebellar lesions can also have lateralized effects on procedural learning. Our objective was to assess the effects of focal cerebellar lesions in procedural learning as measured by the SRTT. We studied 14 patients with single, unilateral vascular lesions in the territory of the posterior-inferior or superior cerebellar artery, who were compared with ten age- and sex-matched controls in a one-handed version of the SRTT. Patients with lesions at any other level of the brain or posterior fossa were excluded by cranial magnetic resonance imaging. Our results show that patients do not acquire procedural knowledge when performing the task with the hand ipsilateral to the lesion, but show normal learning with the contralateral hand. No correlation was found with the side, size, or vascular territory of the lesion. We conclude that procedural learning is impaired in hemispheric cerebellar lesions and involves only the hand ipsilateral to the lesion, which suggests a critical role for the cerebellum and/or crossed cerebellar-prefrontal connections in this type of learning.

Procedural learning is impaired in patients with prefrontal lesions

Objectives: To 1) determine the effect of prefrontal cortex lesions on procedural learning (PL), measured by a serial reaction-time task (SRTT); 2) confirm whether visuomotor PL is lateralized to one hemisphere; and 3) clarify the relation between visuomotor sequence learning and verbal sequence learning, working memory, and executive functions. Background: Previous cognitive neuroscience research has implicated the prefrontal cortex in visuomotor PL but there is a lack of studies examining patients with prefrontal cortex lesions. Methods: We studied 22 patients with strictly unilateral prefrontal cortex lesions (traumatic, ischemic, hemorrhagic, or tumors) and 52 cognitively intact controls matched for age, sex, and educational level. We administered to subjects long (10-item sequence) and short (4-item sequence) versions of the SRTT. With the long version, each hand was evaluated separately. Learning was indicated by the shortening of response times (RT) and decrease in errors across the sequential blocks and, most importantly, the rebound increase in RTs and errors when comparing the last sequence block with the next random block. Frontal lobe functions and verbal sequence learning were also assessed. Results: Patients with unilateral prefrontal cortex lesions show PL impairment that involves both hands, although more errors were observed when the hand contralateral to the lesion was performing. Only those patients whose lesions were >2 cm in diameter were impaired. Neuropsychologic evaluation indicated impaired verbal sequence learning and executive function deficits. Patients with poorer working memory and verbal sequence learning were also more impaired in visuomotor sequence learning. Conclusions: The prefrontal cortex has a role in PL and is part of the neural circuit that mediates this type of learning.

Prefrontal lesions impair the implicit and explicit learning of sequences on visuomotor tasks

Abstract. Objective: (1) To verify whether the prefrontal cortex (PFC) is specifically involved in visuomotor sequence learning as opposed to other forms of motor learning and (2) to establish the role of executive functions in visuomotor sequence learning. Background: Visuomotor skill learning depends on the integrity of the premotor and parietal cortex; the prefrontal cortex, however, is essential when the learning of a sequence is required. Methods: We studied 25 patients with PFC lesions and 86 controls matched for age and educational level. Participants performed: (1) a Pursuit Tracking Task (PTT), composed of a random tracking task (perceptual learning) and a pattern tracking task (explicit motor sequence learning with learning indicated by the decrease in mean root square error across trial blocks), (2) a 12-item sequence version of a serial reaction time task (SRTT) with specific implicit motor sequence learning indicated by the rebound increase in response time when comparing the last sequence block with the next random block, and (3) a neuropsychological battery that assessed executive functions. Results: PFC patients were impaired in sequence learning on the pattern tracking task of the PTT and on the SRTT as compared to controls, but performed normally on the PTT random tracking task. Learning on the PTT did not correlate with learning on the SRTT. PTT performance correlated with planning functions while SRTT performance correlated with working memory capacity. Conclusions: The PFC is specifically involved in explicit and implicit motor sequence learning. Different PFC regions may be selectively involved in such learning depending on the cognitive demands of the sequential task.

Patients with Right Frontal Lesions are Unable to Assess and Use Advice to Make Predictive Judgments

Frontal lobe damage impairs decision-making. Most studies have employed gambling and probabilistic tasks, which have an emotional (reward-punishment) component and found that patients with ventromedial sector lesions have exceptional difficulty performing normally on these tasks. We have recently presented an economic decision-making task to patients and normal volunteers that required them to not only forecast an economic outcome but also to weigh advice from four advisors about the possible outcome across 40 trials. We studied 20 patients with right frontal lobe lesions and 9 patients with parietal lobe lesions and compared their performance to 20 matched controls. Frontal lobe lesion patients were inconsistent at using advice and their forecasts were poor. Patients with dorsolateral but not orbito-frontal lesions showed some ability to assess advice. Patients with parietal lobe lesions were good at assessing advice but were slow at doing so; they were consistent but poor at using advice and their use of advice was unrelated to their forecasting. All three patient groups were overconfident in their own performance. In contrast, controls could both use and assess advice, their ability to use advice was mediated by their ability to assess it, and they were not overconfident. Group differences on an overall measure of accuracy on this task were associated with an ability to accurately plan. Differences in ability to assess and forecast were associated with planning and working memory performance. These findings indicate that patients with both right dorsolateral and orbito-frontal lesions may be impaired when required to make complex decisions related to forecasting and judgment. Our findings enlarge the scope of decision-making deficits seen in patients with frontal lobe lesions and indicate additional circumstances in which patients with frontal lobe lesions will have difficulty in deciding.

Bilateral Vertebral Artery Dissection in a Patient With Afibrinogenemia

BACKGROUND Afibrinogenemia, a rare coagulation disorder, has not been associated with vertebral artery dissections. CASE DESCRIPTION A 28-year-old woman with afibrinogenemia developed spontaneous neck pain followed by a right medullary infarction, and MR angiography showed extensive bilateral vertebral artery dissection. She was treated with fibrinogen replacement and anticoagulants and showed a favorable evolution, with only mild residual right upper arm incoordination. CONCLUSIONS In this patient spontaneous bilateral vertebral artery dissection complicated afibrinogenemia. Since anticoagulant therapy is usually indicated for arterial dissection, this association created a therapeutic problem. This patient received anticoagulants with fibrinogen replacement, which resulted in a favorable evolution.

Response to intravenous lidocaine in a patient with SUNCT syndrome.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) syndrome represents a serious therapeutic and diagnostic challenge, since it is usually refractory to most drugs and lacks biological markers. Response to intravenous lidocaine administration has been reported in some patients while it has failed in others. We report a patient with SUNCT syndrome who showed a clear-cut and consistent response to intravenous lidocaine therapy, which proved superior to placebo in a single-blinded fashion. Intravenous lidocaine should be considered in all patients with SUNCT syndrome. Response to this therapy could represent a diagnostic tool.

The therapeutic paradox in the diagnosis of tuberculous meningitis

The diagnosis of tuberculous meningitis (TBM) is challenging because of the low mycobacterial yield in the CSF and the lack of adequate diagnostic alternatives.1,2 This often places the clinician facing patients with subacute-chronic meningitis in the situation of starting empirical antituberculous therapy while ruling out other etiologies. Adenosine deaminase in the CSF is increased in TBM but has false negatives, and PCR has a less than ideal sensitivity.3 Once anti-mycobacterial therapy is started, some patients with TBM may develop a paradoxical reaction that may give a clue to the correct diagnosis. In this report we characterize a paradoxical response in a patient with subacute lymphocytic meningitis in whom the microbiologic diagnosis remained elusive for almost 4 weeks. A 70-year-old woman was admitted with a 1-week history of general malaise, disorientation, and fever of 37.7 °C. A cranial CT scan (with and without contrast) was normal, and a spinal tap yielded a mononuclear pleocytosis with increased …

Impact of preventive therapy with nadolol and topiramate on the quality of life of migraine patients

Preventive therapy is aimed at reducing migraine frequency, but should also improve the much deteriorated quality of life of the migraneur. We aimed to evaluate the impact of preventive therapy with two widely employed drugs (topiramate and nadolol) on the quality of life of migraine patients. A population of consecutive migraineurs aged ≥16 years, with frequent migraines, was selected prospectively for evaluation at baseline and after 16 weeks of therapy with nadolol or topiramate (40 mg and 100 mg daily, respectively) by generic and specific quality of life questionnaires (SF-36 and MSQOL) and by an anxiety and depression scale (HADS). Preventive therapy resulted in a statistically significant improvement in physical domains of the SF-36, whereas mental domains remained almost unchanged. Despite this improvement, all domains remained below the population norms. The HADS revealed a moderate depressive state at baseline that did not change with therapy. The MSQOL global score also revealed statistically significant improvement. Both drugs were similarly effective, although topiramate was superior on the role physical domain compared with nadolol. Preventive therapy with nadolol and topiramate significantly improves the quality of life of migraineurs, although additional efforts are needed to place them in a nearer-to-normal situation compared with the general population.

Peripheral arterial embolism during thrombolysis for stroke.

Hemorrhage is a possible complication of thrombolytic therapy for brain infarction that carries high morbidity and mortality.1 In fact, most exclusion criteria refer to situations prone to hemorrhage, such as low platelet count, coagulation abnormalities, a recent major surgery, or gastrointestinal bleeding. Unexpected and seemingly paradoxical is the occurrence of a thromboembolic phenomenon in the setting of thrombolytic therapy. We report a patient who was subject to thrombolytic therapy for ischemic stroke with complete neurologic recovery but who presented a lower limb embolism during the administration of IV tissue plasminogen activator (tPA). A 73-year-old man was admitted to the cardiology department of our hospital for left heart failure and a suspicion of dilated myocardiopathy and was successfully treated with diuretics. Twelve hours after admission, he had acute left-sided hemiplegia with hemianesthesia, visual neglect, and anosognosia. The NIH Stroke …

Superior sagittal sinus thrombosis complicating Crohn's disease

utilization of glucose via anaerobic glycolysis is occurring either in the cellular elements of the CSF or in the adjacent neural or meningeal tissues.’ While hypoglycorrhachia is usually accompanied by a pleocytosis, evidence from experimental models of bacterial meningitis and subarachnoid hemorrhage suggests that glycolysis by bacteria, leukocytes, or red blood cells is not sufficient to cause low glucose in the CSF.2-5 Rather, there is probably a disturbance of cerebral metabolism entailing a significantly increased degree of anaerobic glycolysis.4.6 Moreover, hypoglycorrhachia can occur when the pleocytosis is minimal or absent, eg, during recovery from bacterial meningitis or in malignant melanomatosis.’ De Vivo and colleagues7 found evidence for a deficiency in the glucose transporter protein in a 15-month-old infant with persistent hypoglycorrhachia, microcephaly, seizures, and mild developmental delay; however, the CSF lactate was also low. In light of these considerations, it seems likely that increased glucose metabolism by neural tissues, including possibly aerobic as well as anaerobic glycolysis, and not impaired glucose transport, is the primary explanation for the CSF findings in our patient. The present case documents the rare occurrence of persistent aglycorrhachia in the lumbar CSF without a pleocytosis and in the absence of an infectious or neoplastic cause.