Case study: acute basal ganglia enlargement and obsessive-compulsive symptoms in an adolescent boy

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAs) may arise when antibodies directed against invading bacteria cross-react with basal ganglia structures, resulting in exacerbations of obsessive-compulsive disorder (OCD) or tic disorders. This is a report of severe worsening of obsessive-compulsive symptoms in an adolescent boy following infection with group A beta-hemolytic streptococci for whom serial magnetic resonance imaging scans of the brain were acquired to assess the relationship between basal ganglia size, symptom severity, and treatment with plasmapheresis. These data provide further support for basal ganglia-mediated dysfunction in OCD and the potential for immunological treatments in PANDAs patients.     

Neuroanatomical aspects of cognitive-behavioural therapy response in obsessive-compulsive disorder. An evolving perspective on brain and behaviour

BACKGROUND: Recent research has demonstrated that cognitive-behavioural therapy (CBT) for obsessive-compulsive disorder (OCD) can systematically modify cerebral metabolic activity in a manner which is significantly related to clinical outcome. METHOD: A substantial body of research is reviewed which supports an involvement of neural circuitry connecting the orbitofrontal cortex, cingulate gyrus and basal ganglia in the expression of the symptoms of OCD. RESULTS: Data are presented which expand upon previous work demonstrating effects of CBT on functional interactions between limbic cortex and the basal ganglia. CONCLUSIONS: The relevance of these effects of CBT on brain function is discussed in the context of recent advances in our knowledge of cortical-basal ganglia physiology. The clinical importance of these data is best appreciated when they are seen to reflect the interactive nature of the relationships between cognitive choice, behavioural output and brain activity.     

Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder

BACKGROUND: Neuroimaging studies provide strong evidence that the pathophysiology of obsessive-compulsive disorder (OCD) involves abnormal functioning along specific frontal-subcortical brain circuits. METHOD: A literature search was carried out for all brain imaging studies of patients with OCD. We also reviewed the basic science literature on the functional neuroanatomy of cortico-basal ganglia circuits, and integrated this information with neuroimaging data in OCD to formulate a theoretical model of brain mediation of OCD symptoms and response to treatment. RESULTS: At least a subgroup of patients with OCD may have abnormal basal ganglia development. Functional neuroimaging studies indicate that OCD symptoms are associated with increased activity in orbitofrontal cortex, caudate nucleus, thalamus and anterior cingulate gyrus. CONCLUSIONS: OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, perhaps due to an imbalance of tone between direct and indirect striato-pallidal pathways. We present a model which describes how frontal-subcortical brain circuitry may mediate OCD symptomatology, and suggest a hypothesis for how successful treatments may ameliorate symptoms, via their effects on circuit activity.     

Obsessive-compulsive disorder associated with brain lesions: clinical phenomenology, cognitive function, and anatomic correlates

We studied the behavioral, cognitive, and neuroimaging characteristics of obsessive-compulsive disorder (OCD) in 13 patients with focal brain lesions (acquired OCD) and compared their clinical features and the severity of obsessive and compulsive (OC) symptoms with patients with idiopathic OCD. Both OCD groups were further compared with matched normal controls on a series of neuropsychological tests. Patients with acquired OCD had a negative familial history and later age at onset of OCD symptoms than patients with idiopathic OCD. The two OCD groups showed relatively similar clinical phenomenology, severity of OC symptoms, and profile of neuropsychological deficits. Compared with normal control subjects, both OCD groups showed cognitive deficits affecting attention, intellectual function, memory, word retrieval, and motor and executive functions. Eight of the 13 patients with acquired OCD had abnormal neurologic examinations, whereas only 3 of the 13 patients with idiopathic OCD had abnormal neurologic examinations. Neuroimaging in the acquired OCD group disclosed a variety of lesions involving exclusively the cerebral cortex (frontal, temporal, or cingulate regions), the basal ganglia, or both. These results suggest that acquired and idiopathic OCDs may share a common pathophysiologic mechanism, and that structural damage to specific frontal-limbic-subcortical circuits plays an important role in the pathogenesis of acquired OCD.     

Different roles for serotonin in anti-obsessional drug action and the pathophysiology of obsessive-compulsive disorder

BACKGROUND: There is a major role for serotonin in the mechanism of anti-obsessional drug action. Drugs that block uptake of noradrenaline are not effective in the treatment of obsessive-compulsive disorder (OCD), while drugs that potently bock serotonin reuptake are effective. While enhancement of serotonin neurotransmission is clearly involved in the treatment of OCD, the role of serotonin in the pathophysiology of OCD is less clear. METHOD: This paper provides a brief, focused review of the literature regarding treatment of OCD, the effects of drugs with selective action at various serotonin receptors and results of neurotransmitter depletion studies in patients with OCD. RESULTS: Some patients with OCD may experience remission of OCD symptoms during intoxication with psychedelic drugs that have potent 5-HT2A/2C agonist activity. These findings, coupled with results from serotonin depletion studies in depressed and OCD patients, suggest that enhancement of serotonin neurotransmission may underlie both antidepressant and anti-obsessional drug action, although the targeted brain areas may differ. CONCLUSIONS: OCD may not involve a dysfunction of the serotonin system. Rather, it is more likely to involve a dysfunction of specific brain circuits, particularly in the frontal cortex. Modulation of these circuits by serotonin neurons may underlie the specific action of anti-obsessional drugs.     

Verbal and nonverbal memory processing in patients with obsessive-compulsive disorder: Its relationship to clinical variables.

Memory deficits have been reported in several neuropsychological studies of obsessive-compulsive disorder (OCD). Dysfunction in nonverbal memory has been consistently reported, whereas findings on verbal memory are more heterogeneous. The authors studied 50 patients with OCD who were matched for sex, age, educational level, and hand dominance with 50 healthy controls (HC). Cognitive performance in both groups was assessed on verbal and nonverbal memory tasks, and several clinical variables were also assessed in the patient group. Patients with OCD showed a pattern of cognitive dysfunction with alterations in areas of nonverbal memory (recall and recognition), and verbal memory (learning and recall). Older age at onset of OCD was associated with poorer performance on verbal memory tasks. Low scores on some verbal memory tasks were associated with severity of OCD, and nonverbal memory was influenced by depressive symptoms. The study suggests the existence of dysfunction in the execution of verbal and nonverbal memory tasks in OCD; the influence of clinical variables depends on the specific neuropsychological function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The basal ganglia and cognitive pattern generators

This article introduces the notion of cognitive pattern generators and suggests, by analogy with the central pattern generators of the motor system, that these pattern generators operate to organize neural activity underlying aspects of action-oriented cognition. It is further proposed that the basal ganglia are involved in the control of cognitive as well as motor pattern generators. Disorders of the basal ganglia may thereby contribute to neural circuit dysfunctions that are expressed as positive and negative symptoms of schizophrenia.     

Short-term control of GABA synthesis in brain

Frontal lobe and basal ganglia lesions have been associated with similar cognitive impairments, although their specialized roles in behavior are likely to be different. We examined whether these structures mediate distinctive or overlapping aspects of a complex behavioral process that has been associated with both neural sites, i.e. cognitive flexibility. Patients with focal ischemic lesions to the frontal lobe and basal ganglia were compared on two forms of cognitive flexibility: (1) shifting response set (i.e. reactive flexibility), and (2) producing a diversity of ideas (i.e. spontaneous flexibility). Results indicated that frontal lobe and basal ganglia damage each caused a similar degree of impairment in reactive flexibility, both groups performing at a significantly lower level than posterior cortical lesion and normal comparison groups. However, frontal lobe damage markedly disturbed spontaneous flexibility, while performance after basal ganglia lesion was significantly higher and comparable to posterior cortical lesions. Findings suggest that the frontal lobe and basal ganglia participate differently in the neural substrate of cognitive flexibility. The frontal lobe appears to mediate spontaneous flexibility. The production of diverse ideas may require direct cortical-cortical interactions by the frontal lobe in order to access knowledge systems with novel strategies that transcend the most common semantic linkages. In contrast the corticostriate system appears to mediate reactive flexibility, as the frontal lobe, basal ganglia and their interconnections are required for its operation.     

Osteochondritis dissecans of elbow, ankle and hip: a comparison survey

In 36 patients treated for osteochondritis dissecans (OCD) of the elbow, ankle and hip during a period of 20 years in the same hospital, trauma seems to have been the main etiologic factor in about half of the patients. The first symptoms of the lesions occurred when the patients were between 15 and 20 years of age. Osteochondritis dissecans of the elbow was seen in 19 men. Osteochondritis dissecans in the ankle occurred in 6 men and 5 women. Osteochondritis dissecans in the hip appeared in 5 men and one woman. The first symptoms were pain and restriction of joint movement. Conservative treatment was satisfactory for about one-half of the patients. When operative treatment was indicated, extirpation of loose bodies or loosening fragments was the treatment of choice in OCD of the elbow and ankle. Fixation of the fragment gave satistfactory results in some cases of OCD of the hip. Late results were excellent in only about one-half of the patients. Osteoarthritic changes appeared in the hip, elbow, ankle, in order of decreasing frequency.     

Neural dynamics of short and medium-term motor control effects of levodopa therapy in Parkinson's disease

A neural network model of movement control in normal and Parkinson's disease (PD) conditions is proposed to simulate the time-varying dose-response relationship underlying the effects of levodopa on movement amplitude and movement duration in PD patients. Short and long-term dynamics of cell activations and neurotransmitter mechanisms underlying the differential expression of neuropeptide messenger RNA within the basal ganglia striatum are modeled to provide a mechanistic account for the effects of levodopa medication on motor performance (e.g. the pharmacodynamics). Experimental and neural network simulation data suggest that levodopa therapy in Parkinson's disease has differential effects on cell activities, striatal neuropeptides, and motor behavior. In particular, it is shown how dopamine depletion in the striatum may modulate differentially the level of substance P and enkephalin messenger RNA in the direct and indirect basal ganglia pathways. This dissociation in the magnitude and timing of peptide expression causes an imbalance in the opponently organized basal ganglia pathways which results in Parkinsonian motor deficits. The model is validated with experimental data obtained from handwriting movements performed by PD subjects before and after medication intake. The results suggest that fine motor control analysis and network modeling of the effects of dopamine in motor control are useful tools in drug development and in the optimization of pharmacological therapy in PD patients.     

Effectiveness of exposure and ritual prevention for obsessive-compulsive disorder: Randomized compared with nonrandomized samples.

The efficacy of exposure and ritual prevention (EX/RP) for reducing symptoms of obsessive-compulsive disorder (OCD) has been demonstrated in several randomized controlled trials (RCTs). However, procedures used in these studies to maximize experimental control may have limited their generalizability to typical clinical practice. Treatment outcome data from 110 clinical patients receiving EX/RP on an outpatient fee-for-service basis were compared with findings from 4 RCTs of EX/RP. Adult patients in the clinical sample were not excluded because of treatment history, concomitant pharmacotherapy, psychiatric comorbidity, age, or OCD severity. Clinical patients achieved substantial and clinically meaningful reductions in their OCD and depressive symptoms following EX/RP, which were comparable with those reported in the RCTs. Findings indicate that EX/RP is a potent treatment for OCD, and its benefits are not limited to select patient samples. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of Parkinsonism on motor control

Parkinson's disease, which pathology results predominantly from nigros triatal pathway damage, has been associated with motor dysfunction due to basal ganglia impairment. It is argued that the variability seen within and between individual patients through the course of this neurological disorder may result from abnormal non-uniform neurotransmitter levels as well as functional segregation of neural populations in the basal ganglia. We review evidence that the wide spectrum of motor impairments observed in Parkinsonism may be due to a reduced capability of neurochemical modulation of pallido-thalamocortical activities that impairs movement implementation and execution.     

Mental-rotation deficits following damage to the right basal ganglia.

The authors report the case of a woman with a right basal ganglia lesion and severe mental-rotation impairments. She had no difficulty recognizing rotated objects and had intact left-right orientation in egocentric space but was unable to map the left and right sides of external objects to her egocentric reference frame. This study indicates that the right basal ganglia may be critical components in a cortico-subcortical network involved in mental rotation. We speculate that the role of these structures is to select and maintain an appropriate motor program for performing smooth and accurate rotation. The results also have important implications for theories of object recognition by demonstrating that recognition of rotated objects can be achieved without mental rotation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Improvement of albendazole efficacy against enteral, but not against parenteral stages of Trichinella spiralis by preparing solid dispersions in polyvinylpyrrolidone

Fhar's disease is a rare idiopathic CNS pathology characterized by widespread calcifications of the basal ganglia, cerebellar nuclei and endocranial vessels. The origin of this disease is unknown and a lack of thyroid and parathyroid pathologies is the main statement. From the clinical point of view, extrapyramidal manifestations are common while vertigo and equilibrium disorders are rare. In the present case vertigo and disequilibrium were the main symptoms. Fhar's disease was diagnosed by CT and MRI showing calcification of the basal ganglia without any metabolism disorders or thyroid and parathyroid pathology. A battery of neurotological tests showed alterations of VOR and ocular movement. In particular the saccades movements showed significant hypometria while the smooth-pursuit showed gain diminution and corrective saccades. These anomalies imply dysfunction of sub-cortical centers regulating and modulating ocular movement. VOR alterations included both qualitative anomalies of nystagmus (i.e. dysrhythmia, square waves) and quantitative alterations (i.e. bilateral deficit response to caloric and rotatory stimuli). These alterations could be due to the impairment of cerebellum-vestibular and vestibular-thalamic pathways. Acoustic evoked potentials (ABR, MLR) ruled out central acoustic pathway dysfunction.     

The basal ganglia: focused selection and inhibition of competing motor programs

The basal ganglia comprise several nuclei in the forebrain, diencephalon, and midbrain thought to play a significant role in the control of posture and movement. It is well recognized that people with degenerative diseases of the basal ganglia suffer from rigidly held abnormal body postures, slowing of movement, involuntary movements, or a combination of these a abnormalities. However, it has not been agreed just what the basal ganglia contribute to normal movement. Recent advances in knowledge of the basal ganglia circuitry, activity of basal ganglia neurons during movement, and the effect of basal ganglia lesions have led to a new hypothesis of basal ganglia function. The hypothesis states that the basal ganglia do not generate movements. Instead, when voluntary movement is generated by cerebral cortical and cerebellar mechanisms, the basal ganglia act broadly to inhibit competing motor mechanisms that would otherwise interfere with the desired movement. Simultaneously, inhibition is removed focally from the desired motor mechanisms to allow that movement to proceed. Inability to inhibit competing motor programs results in slow movements, abnormal postures and involuntary muscle activity.     

Pulmonary manifestations in cement workers in Jordan

The literature on obsessive-compulsive disorder (OCD) in children and adolescents is reviewed. The disorder is characterized by obsessions (recurrent troublesome thoughts) and compulsions (ritualized thoughts or behaviors performed repetitively in response to an irresistible urge). OCD is far more common among children and adolescents than was previously believed. Good epidemiological studies from different parts of the world are still needed to determine if prevalence is equally high. Boys seem to have an earlier age of onset of OCD than girls. Male female ratio changed with age of onset, with males predominating in early onset and increasing numbers of females occurring during adolescence. Increasing evidence supports a neurobiological theory for etiology of OCD, specifically a frontal lobe--basal ganglia dysfunction.     

Compulsions developing into command hallucinations

Intrusive, uncontrollable and bizarre thoughts occur in both obsessive-compulsive disorder (OCD) and psychosis. The origin of these mental phenomena and the relationship between them is unclear. A case is described in which long-standing compulsions and the associated resistance temporarily developed the characteristics of command hallucinations, in the absence of any other psychotic symptoms. The implications for psychopathological theories of hallucinations are discussed.     

Is apathy a valid and meaningful symptom or syndrome in Parkinson's disease? A critical review.

Objective: To review the nearly 30 papers suggesting that apathy may occur frequently in Parkinson's disease (PD) and that it may be a symptom or syndrome that is separate from depression. Method: Literature review. Results: The review revealed three possible explanations for the high rates of apathy found in PD. First, there is much interest in an endogenous explanation of apathy because the basal ganglia and dopamine are implicated in both PD and apathy. Researchers have suggested links between apathy, dopamine depletion, and basal ganglia dysfunction in PD. Second, apathy in PD may be exogenous, resulting from disability and activity restriction. Third, apathy findings are inflated due to conceptual problems and methodological confounds. Indeed, apathy may be consistently confounded with symptoms of PD, including expressive masking, depression, disability, and cognitive decline. Conclusion: Because apathy has not yet been found to relate to meaningful patient outcomes, and it appears that other factors such as depression and cognition are more strongly related to quality of life than apathy, there is not enough evidence to conclude that apathy is a clinically meaningful syndrome in PD. The role of PD in motivation is of theoretical and practical interest and deserves further research. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Meige's syndrome associated with basal ganglia and thalamic functional disorders

Magnetic resonance imaging (MRI) or single positron emission computed tomography (SPECT) or both were performed and the responses of surface electromyography (EMG) were examined in seven cases of Meige's syndrome. MRI or SPECT or both demonstrated lesions of the basal ganglia, the thalamus, or both in five of the cases. Surface EMG revealed abnormal burst discharges in the orbicularis oculi and a failure of reciprocal muscular activity between the frontalis and orbicularis oculi in all the cases. These findings suggest that voluntary motor control and reciprocal activity in the basal ganglia-thalamocortical circuits are impaired in Meige's syndrome. In addition, good responses were seen to clonazepam, tiapride and trihexyphenidyl in these cases. Therefore, we conclude that dopaminergic, cholinergic, and gamma-aminobutyric acid (GABA) ergic imbalances in the disorders of the basal ganglia and thalamus in Meige's syndrome cause control in the excitatory and inhibitory pathways to be lost, resulting in the failure of integration in reciprocal muscular activity and voluntary motor control. This failure subsequently causes the symptoms of Meige's syndrome.     

Decision making and set shifting impairments are associated with distinct symptom dimensions in obsessive-compulsive disorder.

Obsessive- compulsive disorder (OCD) is clinically heterogeneous. The authors examined how specific OCD symptom dimensions were related to neuropsychological functions using multiple regression analyses. A total of 39 OCD patients and 40 controls completed the Iowa Gambling Task (IGT; A. Bechara, A. R. Damasio, H. Damasio, & S. W. Anderson, 1994), which is a test of decision making, and the Wisconsin Card Sorting Test (R. K. Heaton, 1981), which is a test of set shifting. OCD patients and controls showed comparable decision making. However, patients with prominent hoarding symptoms showed impaired decision making on the IGT as well as reduced skin conductance responses. OCD patients had poorer set shifting abilities than controls, and symmetry/ordering symptoms were negatively associated with set shifting. These results help explain previous inconsistent findings in neuropsychological research in OCD and support recent neuroimaging data showing dissociable neural mechanisms involved in mediating the different OCD symptom dimensions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)