Frontal Syndrome Research Articles

Giant pituitary tumors secreting growth hormone in children and adolescents

Introduction Pituitary tumors secreting growth hormone (GH) are relatively rare in children and adolescents. Giant ones (maximal diameter ≥ 4 cm) are even rarer. We aimed to analyze their frequency and their complications in Algerian population. Methods It is a retrospective and multicenter study over a long period of time (1980–2013) which aimed to collect giant pituitary tumors secreting GH in order to analyze their characteristics. Results Among 31 well proved somatotroph adenomas observed in children and adolescents (≤ 20 years old) or in older subjects with lack of pubertal development, we found 12 giant tumors = 38.7%. Median age at diagnosis was 22.4 years old (13–30). Eight on 12 suffered from gigantism (66.6%) other had acromegaly. Median tumor diameter = 60.5 mm (40–100). Median GH = 570 ng/mL (30–1430). All had moderate to severe visual troubles. Two or more pituitary deficits were observed in 4 cases = 33.3%, hydrocephalus = 8 cases (66.6%), frontal syndrome = 3 = 25% and epilepsy n = 1 = 8.3%. Conclusion In our population giant tumors secreting GH are frequent and diagnosed late even in those with gigantism which explains the high frequency of severe and life threatening neurological complications.

An evaluation of antisocial behaviour in children after traumatic brain injury: the prospect of improving the quality of life in rehabilitation.

The aim of the article is to present the consequences of traumatic brain injury in children, associated with general cognition and behavioural disorders, mainly of the antisocial type. A total of 20 school-age children took part in the study, including six girls and 14 boys. The average age of the children was 13.35 years (standard deviation SD = 1.95). The research instruments included an analysis of documentation, a structured clinical interview, MMSE and Frontal Behavioral Inventory (FBInv) with additional set of five supplementary questions directed for detection of antisocial behavior. The research was conducted from the beginning of January 2009 until the end of May 2009. As hypothesized, the functioning of the children with traumatic brain injury is severely disrupted, because of the presence of cognitive impairment, however, dementia is not manifested. In a significant number of the children with traumatic brain injury we found not only the frontal syndrome, but also the occurrence of antisocial behaviour. The most commonly reported behavioural problems were: disorganization commonly referred to as laziness, hypersensitivity, and anxiety. The most common types of anti-social behaviour were: impulsivity, physical and verbal aggression, and also an outburst of anger. The children with traumatic brain injury suffer from a cognitive disorders and behavioural problems, especially impulsivity, physical and verbal aggression, increased anxiety, and disorganization. The occurrence of frontal syndrome is related to the development of antisocial behaviour.

Diagnosis and Treatment of Corticobasal Degeneration

Corticobasal degeneration is a pathologic entity. Presenting clinical phenotypes include corticobasal syndrome (CBS), frontal behavioral spatial syndrome, aphasia, progressive supranuclear palsy-like syndrome (PSPS), and a predominantly cognitive phenotype often mistaken for Alzheimer's disease (AD). Treatment of CBD is symptomatic, particularly given recently negative neuroprotective studies. Given the relentless progression in CBD, all interested patients should be offered the opportunity to enroll in clinical neuroprotective trials as they arise. For symptomatic therapy, treatment options are necessarily based on evidence from other disorders given the lack of studies in CBD. In patients with CBS and PSPS, parkinsonism is treated with levodopa/carbidopa. This generally has modest and transient benefits at best and often results in no improvement. Botulinum toxin injections are the treatment of choice for limb dystonia. Clonazepam and levetiracetam are commonly used for myoclonus. Physical therapy is an important part of motor treatment, particularly for fall prevention strategies and assist device assessment. Whether medications such as cholinesterase inhibitors or memantine have any role in CBD is unclear given the various responses described in related phenotypes and diseases. Treating the behavioral symptoms associated with CBD is critical in an attempt to treat symptoms for which we have good pharmacologic interventions and to hopefully improve quality of life. General supportive care is important, including assessing for sores related to dystonia or immobility, monitoring dysphagia, and identifying needs for support services. Finally, as with other relentlessly progressive neurodegenerative diseases, it is critical to provide family and caregiver support and to assess for when palliative care services will serve the patient best.

Recovery and outcome of frontal alien hand syndrome after anterior cerebral artery stroke

Ischemic lesions within the territory of the anterior cerebral artery present with a variety of clinical signs and symptoms. Among these, frontal alien hand syndrome is rare and easily overlooked in the acute clinical setting, but significantly impacts on functional activities of daily life. Given its rareness, very little is known about its long-term outcome. To shade some more light onto this issue, clinical presentation, course of rehabilitation and outcome of two illustrative cases of frontal alien hand syndrome following anterior cerebral artery stroke are presented. Within seven and nine months from symptom onset, respectively, the clinical symptoms of frontal alien hand had resolved completely in both cases. We conclude that frontal alien hand syndrome has a favourable long-term outcome.

Thalamocortical Connections between the Mediodorsal Nucleus of the Thalamus and Prefrontal Cortex in the Human Brain: A Diffusion Tensor Tractographic Study

PurposeThe elucidation of thalamocortical connections between the mediodorsal nucleus (MD) of thalamus and the prefrontal cortex (PFC) is important in the clinical fields of neurorehabilitation and psychiatry. However, little is known about these connections in human brain. We attempted to identify and investigate the anatomical characteristics of the thalamocortical connection between MD and PFC in human brain using diffusion tensor tractography (DTT).Materials and MethodsThirty-two healthy volunteers were recruited for this study. Diffusion tensor images were scanned using a 1.5-T. A seed region of interest was placed at the MD of the thalamus on coronal images, and target regions of interest were placed on the dorsolateral prefrontal cortex (DLPFC), the ventrolateral prefrontal cortex (VLPFC), and the orbitofrontal cortex (OFC), respectively. The three thalamocortical connections found were reconstructed using Functional Magnetic Resonance Imaging of the Brain (FMRIB) software.ResultsThe three thalamocortical connections were arranged in subcortical white matter in the following order from upper to lower levels: the DLPFC, the VLPFC, and the OFC. In terms of fractional anisotropy and mean diffusivity values, no significant differences were observed between the DLPFC, VLPFC and OFC (p>0.05). In contrast, the OFC tract volume was higher than those of the DLPFC and the VLPFC (p<0.05).ConclusionThree thalamocortical connections were reconstructed between MD and PFCs in human brain using DTT. We believe that the results of this study would be helpful to clinicians in treating frontal network syndrome and psychiatric diseases.

EEG Abnormalities In ADHD: How Should We Treat?

Copyright: © 2013 Kanemura H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Prevailing opinion characterizes ADHD as a disorder of executive function attributable to abnormal dopamine transmission in the frontal lobes and frontostriatal circuitry. Thus, ADHD can be characterized by frontal lobe dysfunction. The onset of paroxysmal electrical activity was closely related in time with the development of a neuropsychological and behavioral pattern characterized by inattention, impulsiveness, mood swings and perseveration, with deficits in time orientation, reasoning and learning strategies, which shared many features with adult frontal syndrome [18]. In ADHD with EEG abnormalities, paroxysmal activity affects the frontal area and results in those impairments. Damage to the prefrontal cortex has been associated with an inability to organize and carry out goal-directed behaviors. In our previous 3-dimensional MRI volumetric studies, frontal and prefrontal lobe volumes revealed growth disturbance in epilepsy patients with frontal lobe dysfunction compared with those of normal subjects [19,20]. Moreover, in the patients with shorter seizure durations and EEG abnormalities periods, ratios were soon restored to a more normal growth ratio, whereas growth disturbances of the prefrontal lobes were persistent in the patients with longer seizure durations and EEG abnormalities periods. These findings suggest that the duration of EEG paroxysmal anomalies may be associated with prefrontal lobe growth, which is associated with neuropsychological problems. Damage to the frontal regions during childhood may interrupt normal maturational processes and organization, resulting in impairments to neurobehavioral development. Integrative executive functions may thus rely on the health of frontal lobe tissue and connectivity with the rest of the cortex [21].

Assessing Frontal Behavioral Syndromes and Cognitive Functions in Traumatic Brain Injury

This study examined the relationship between individual and family ratings on a measure of frontal behaviors using the Frontal Systems Behavior Scale (FrSBe). Additionally, this study investigated whether self-reported symptoms of frontal-lobe dysfunction correspond to neuropsychological performance, particularly those tests measuring executive functions. Thirty-three individuals with moderate-to-severe traumatic brain injury (TBI) and 19 healthy individuals completed the FrSBe and neuropsychological measures. Results indicated that the self-ratings of individuals’ apathy, disinhibition, and executive dysfunction significantly increased from before to after injury, as did the family members’ ratings, with no significant difference between the patients’ and family members’ reports for any of the three FrSBe subscales. Although individuals with TBI demonstrated impairments in neuropsychological measures, including measures of executive functioning, few significant correlations were found between the patients’ FrSBe ratings and measures of cognitive functioning. This suggests that information from the FrSBe may differ from information gathered during a cognitive evaluation and may enhance our understanding of the behavioral sequelae following TBI that may not be captured by neuropsychological assessment alone.

Overweight after traumatic brain injury: Frontal syndrome or endocrine disorder?

Overweight after traumatic brain injury: Frontal syndrome or endocrine disorder?

The panoply of field-dependent behavior in 1436 stroke patients. The mirror neuron system uncoupled and the consequences of loss of personal autonomy

Evaluation of the multifaceted nature of frontal network syndromes is uniquely challenging and rarely tested in the acute/sub-acute stroke period. Field-dependent behavior such as imitation behavior, utilization behavior, and environmental dependency syndrome, as a component of altered environmental autonomy, may be a reliable bedside test. This research focused on the frequency of field-dependent behavior in stroke, the subtypes and relation to frontal lobe lesion location and stroke etiology. A validated frontal network score incorporating a 10-point imitation behavior scale was applied to alert patients without significant aphasia, encephalopathy, dementia, or substance abuse. Discriminative validity assessment with magnetic resonance imaging, diffusion weight imaging (MRI-DWI brain) was performed and correlational validity was established using standard neuropsychological tests. Of the stroke patients (n = 1436), those with frontal network symptoms (335/1203; 28%) were analyzed further. In the 73 patients with lesions restricted to the frontal lobes or the frontal subcortical circuits, 56 complied with the 10-point imitation behavior scale testing. Forty-five of 56 (80%) demonstrated imitation behavior (sensitivity 73% and specificity 94%). Correlational validity testing with four commonly used frontal lobe neuropsychological tests was good. The stroke etiology included 26 (59%) “other” causes, 9 (20%) intracerebral hemorrhages, 3 (7%) cardioembolic causes, 3 (7%) large vessel disease, 2 (4%) small vessel disease, and 2 (4%) unknown etiology. Field-dependent behaviour subtypes included imitation behavior (n = 45), utilization behavior (n = 9), environmental dependency syndrome (n = 4), and complex other forms of environmental dependence syndrome (n = 5). It was concluded that imitation behavior is a relatively common occurrence with lesions in the frontal lobes in the acute/sub-acute stroke period and is associated predominantly with non-mainstream (other) stroke causes and intracerebral hemorrhage.

Psychiatric manifestations in cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is a rare and severe, but treatable, inborn disorder of bile acid biosynthesis and sterol storage with autosomal recessive inheritance and variable clinical presentation. CTX treatment consists of chenodeoxycholic acid and must be started as early as possible to prevent permanent disability. Psychiatric manifestations are rare and non-specific, and often lead to significant diagnostic and treatment delay. Therefore, better recognition of the gamut of psychiatric manifestations in CTX can diminish the risk of misdiagnosis and irreversible neurological deterioration. We hereby describe the psychiatric features in CTX. A complete review of all published cases of CTX in the medical literature was undertaken and the case reports with psychiatric presentation were collected and analyzed. We also describe the psychiatric features in relation to the neurological semeiology in six patients with CTX diagnosed at the La Salpêtrière Hospital. We conclude that psychiatric manifestations in CTX follow a bimodal/bitemporal pattern, appearing early in the disease course in the form of a behavioral/personality disorder associated with learning difficulties or mental retardation, or manifesting in advanced disease in the setting of dementia as rich neuropsychiatric syndromes, such as frontal, orbitofrontal or frontotemporal syndromes of cortico-subcortical dementia encompassing behavioral/personality disturbance, affective/mood disorders or psychotic disorders. Behavioral/personality disturbance in childhood or adolescence, especially when accompanied by learning difficulties, should therefore lead to further investigation to exclude CTX, as early diagnosis and treatment is critical for prognosis.

A case of bilateral frontal tumors without “frontal syndrome”

We report the longitudinal case study of a right-handed patient harboring two frontal tumors that benefited from bilateral simultaneous surgery. The tumors were WHO Grade II gliomas located in the left inferior frontal area (including the cingulate gyrus) and the right anterior superior frontal gyrus. The double tumor resection was guided by direct electrical stimulation of brain areas while the patient was awake. Neuropsychological assessments were administered before and after the surgery to analyse how the brain functions in the presence of two frontal gliomas that affect both hemispheres and reacts to a bilateral resection, which can brutally compromise the neuronal connectivity, progressively established during the infiltrating process. We showed that both the tumor infiltration and their bilateral resection did not lead to a “frontal syndrome” or a “dysexecutive syndrome” predicted by the localization models. However, a subtle fragility was observed in fine-grain language, memory and emotional skills. This case study reveals the significance of brain plasticity in the reorganization of cognitive networks, even in cases of bilateral tumors. It also confirms the clinical relevance of hodotopical brain models, which considers the brain to be organized in parallel-distributed networks around cortical centers and epicenters.

Connectivity-Based Parcellation of the Thalamus Explains Specific Cognitive and Behavioural Symptoms in Patients with Bilateral Thalamic Infarct

A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F.) had a pervasive deficit in episodic memory, but only one of them (R.F.) suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI) scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients’ lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P.) implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC). Conversely, R.F.’s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.’s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient’s frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal lesions on interconnectivity brain patterns.

Frontal network syndrome testing: clinical tests and positron emission tomography brain imaging help distinguish the 3 most common dementia subtypes.

Dementia diagnosis and the various subtypes are challenging in the absence of biomarkers. To examine available tests and neuroimaging procedures that may help distinguish these disorders. Alzheimer's disease (AD), cognitive vascular disorder (CVD), and Frontotemporal lobe disorders (FTLD) were tested with a hierarchical neuropsychological battery that included the Frontal Systems Behavior Scale, Mini-Mental State Examination, Montreal Cognitive Assessment Test, and subtests. All patients had multimodality magnetic resonance imaging and (18)F fluorodeoxyglucose-positron emission tomography (FDG-PET) brain scans. Of the 161 patients evaluated for dysmemory and cognitive impairment, 31 satisfied the full protocol. The mean T scores for the 3 principal frontal system syndromes for the AD group were all abnormal save disinhibition. For the CVD and FTLD groups, all the 4 subcategory scores were abnormal. Disinhibition differed significantly between the AD and FTD group (analysis of variance [ANOVA], P = .02) and there was a strong association between the memory for 5 words test and a significant difference in the word list generation test score among the 3 groups (ANOVA, P = .0233). There was a strong association between the FDG-PET and the disease subtype (P < .0001). Evaluation for disinhibition, word list generation, 5-word memory testing and PET brain imaging may help distinguish the 3 most common dementia subtypes.

The human frontal lobes and frontal network systems: an evolutionary, clinical, and treatment perspective.

Frontal lobe syndromes, better termed as frontal network systems, are relatively unique in that they may manifest from almost any brain region, due to their widespread connectivity. The understandings of the manifold expressions seen clinically are helped by considering evolutionary origins, the contribution of the state-dependent ascending monoaminergic neurotransmitter systems, and cerebral connectivity. Hence, the so-called networktopathies may be a better term for the syndromes encountered clinically. An increasing array of metric tests are becoming available that complement that long standing history of qualitative bedside assessments pioneered by Alexander Luria, for example. An understanding of the vast panoply of frontal systems' syndromes has been pivotal in understanding and diagnosing the most common dementia syndrome under the age of 60, for example, frontotemporal lobe degeneration. New treatment options are also progressively becoming available, with recent evidence of dopaminergic augmentation, for example, being helpful in traumatic brain injury. The latter include not only psychopharmacological options but also device-based therapies including mirror visual feedback therapy.

Neurological and neuropsychological deterioration in artisanal gold miners from the town of Andacollo, Chile

It is widely known that human exposure to mercury vapor can cause neurological and neuropsychological deterioration. We have investigated if a population of Chilean artisanal gold-mining workers heavily exposed to elemental mercury (Hg0) display neurological and neuropsychological impairment. Male volunteers occupationally exposed to Hg0 (“gold miners”, n = 35) were recruited and compared with a group of unexposed workers (n = 40). Blood specimens were obtained from both groups for total mercury quantification. Upon neurological examination, 71% of the “gold miners” group showed abnormalities expressed as frontal impairment, tremor, or simultaneously frontal impairment, parkinsonism, and pyramidal syndrome. In contrast, only 16% of the individuals in the control group displayed neurological abnormalities. The “gold miners” group also showed impairment of the neuropsychological performance and the distribution of abnormal scores for almost all the neuropsychological tests applied was significantly higher in this group compared to the control group. Educational level, alcohol intake, and smoking habits did not influence the outcome of the neurological or neuropsychological examinations. Finally, despite that the higher blood mercury concentrations were found in the “gold miners” group, they were not significantly different from the values obtained in the control group.

Criteria for the diagnosis of corticobasal degeneration

Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset ≥ 50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed.

Nephrotic syndrome associated with meningioma

A 58-year-old man presented with recurrent frontal meningioma and nephrotic syndrome. Renal biopsy could not be done in view of the rapid neurological deterioration. The patient underwent surgical resection of the tumor. Within 4 weeks, the edema decreased, serum albumin improved, and proteinuria decreased spontaneously. At three months of followup, the patient had attained complete remission of nephrotic state.

Callosal Disconnection Syndrome after Corpus Callosum Infarct: A Diffusion Tensor Tractography Study

We report a patient who presented with callosal disconnection syndrome (CDS) and fiber disconnection on diffusion tensor tractography (DTT) after an infarct of the corpus callosum (CC). A 72-year-old woman presented with manifestations of CDS, including frontal alien hand syndrome (AHS), left agraphia, right hemiparesis, right somatosensory deficit, left neglect, and impaired visual recognition. DTT was performed for the evaluation of CC fibers, followed by comparison with DTT findings of normal subjects. DTT of the normal subject revealed bilateral extension of CC fibers to the frontal, parietal, and occipitotemporal cortices. By contrast, CC fibers of the patient revealed extensive disruption, with the exception of CC fibers passing through the anterior genu and the posterior splenium. The extensive disruption of CC fibers appears to explain the patient's various CDS symptoms. In brief, DTT could be useful for detection of CC lesions in patients with CDS.

Fronto-striatal dysfunction in type 3 familial cortical myoclonic tremor epilepsy occurring during aging

The aim of this work is to study the cognition, progressive gait impairment, and neuroimaging findings in two patients over 65 years old of the previously described type 3 familial cortical myoclonic tremor with epilepsy (FCMTE3). We report investigations in two of these five FCMTE3 subjects over 65 and showing progressive gait disorders. They both had a pseudo-Parkinson's way of walking and visual intolerance to bright light and brightness contrast without EEG abnormalities exacerbating cortical myoclonus or triggering seizure. Case 1 had moderate gait impairment and a severe frontal syndrome. Case 2 had severe gait impairment and diffuse cognitive disorders. Both cases had cortical hypoperfusion (predominantly in the left frontal lobe) and no cerebellar abnormality on cerebral perfusion SPECT. DAT-SPECT showed dopaminergic depletion. These data indicate fronto-striatal dysfunction associated with gait impairment and cognitive disorders appearing after several decades of disease progression. This gives clues to understanding the pathogenesis and evolution of FCMTE3. Permanent myoclonic discharges or long-term valproate treatment may cause significant toxic effects on neurons (dopaminergic and frontal neurons). Further functional and molecular analyses are required in order to better understand this pathology and the consequences of chronic cortical myoclonus.

VALUES † : A National Multicenter Study of Regional and Gender Differences in Frontotemporal Disease in Amyotrophic Lateral Sclerosis

SUMMARY Aims: To investigate regional and gender differences in prevalence rates and the pattern of cognitive and behavioral impairment in amyotrophic lateral sclerosis. Materials &amp; methods: One hundred and ten subjects (55 male) from 14 amyotrophic lateral sclerosis clinics were cross-sectionally evaluated with the Penn State Brief Exam of frontal and temporal dysfunction syndromes. Results: Prevalence rates of cognitive impairment and behavioral impairment were statistically equivalent among rural, suburban and urban subgroups. Females evidenced significant strengths in fluency and limitations in configurational processing. Patterns of regional findings suggested greater frontal cortical involvement in the rural sample. Females demonstrated more bihemispheric involvement in comparison to more left hemispheric involvement for males. Conclusions: Regional prevalence differences in frontotemporal disease prodrome appear insignificant and multifactorial, while being consistent with the toxicity model implicating pesticides in frontal lobe change. Female gender potentially masks the frontotemporal disease prodrome due to a bilateral distribution of language processing, which requires an assessment of right hemisphere-mediated capacities to detect.