Frontal Lobe Syndrome


Article Author:
Letitia Pirau


Article Editor:
Forshing Lui


Editors In Chief:
Eric Flake


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
12/19/2018 6:35:24 AM

Introduction

Neuroanatomically, the frontal lobe is the largest lobe of the brain lying in front of the central sulcus. It is divided into 3 major areas defined by their anatomy and function. They are the primary motor cortex, the supplemental and premotor cortex, and the prefrontal cortex. Damage to the primary motor, supplemental motor, and premotor areas lead to weakness and impaired execution of motor tasks of the contralateral side. The inferolateral areas of the dominant hemisphere are the expressive language area (Broca area, Brodmann areas 44 and 45), to which damage will result in a non-fluent expressive type of aphasia. Frontal lobe syndrome, in general, refers to a clinical syndrome resulting from damage, and impaired function of the prefrontal cortex, which is a large association area of the frontal lobe. The areas involved may include the anterior cingulate, the lateral prefrontal cortex, the orbitofrontal cortex, and the frontal poles.

Frontal lobe syndrome is a broad term used to describe the damage of higher functioning processes of the brain such as motivation, planning, social behavior, and language/speech production. Although the etiology may range from trauma to neurodegenerative disease, regardless of the cause frontal lobe syndrome poses a difficult and complicated condition for physicians. Classically considered unique among humans, the frontal lobes are involved in a variety of higher functioning processing, such as regulating emotions, social interactions, and personality. The frontal lobes are critical for more difficult decisions and interactions that are essential for human behavior. However, with the spread of neurosurgery and procedures such as lobotomy and leucotomy for treatment of psychiatric disorders, a variety of cases have illustrated the significant behavioral and personality changes due to frontal lobe damage. Harlow first described this collection of symptoms as "frontal lobe syndrome" after his research on the famous Phineas Gage who suffered a dramatic change in behavior as a result of trauma. Thus, an abnormality in the frontal lobe could dramatically change not only processing but personality and goal-oriented directed behavior.

Prior research has sought to identify the major areas where lesions may occur to cause the behavioral changes in frontal lobe disorders.

Ventromedial Orbitofrontal Cortex

Commonly known to cause “frontal lobe personality”, lesions in the orbitofrontal areas classically cause dramatic changes in behavior leading to impulsivity and a lack of judgment. Lesions are usually found in Broadmann’s Areas 10, 11, 12, and 47 is associated with a loss of inhibition, emotional lability, and inability to function appropriately in social interactions. The most popular case involving a lesion in this area is the case of Phineas Gage who had major behavioral changes after his trauma. However, in a study by Tranel and Damasio et al., a variety of other etiologies such as stroke and neoplasms may cause “frontal lobe personality.”[1][2]

Anterior Cingulate and Dorsolateral Syndromes

Lesions in the areas around Brodmann areas 9 and 46 may cause deficits within working memory, rule-learning, planning, attention, and motivation.[3] Recent studies have reinforced that DLPFC is critical for working memory function and in particular for monitoring and manipulating the content of working memory. DLPFC may also affect attention as several cases have documented patients complaining of attentional deficits after brain trauma.[4] There are also psychiatric implications due to injury to DPFMC. Previous studies have researched how lesions in the DLPFC may cause "pseudo-depressive" syndrome associated with DLPFC associated with a loss of initiative, decreased motivation, reduced verbal output, and behavioral slowness (abulia). Other processing issues include rule learning, task switching, planning/ problem solving, and novelty detection and exogenous attention.[3][5] The anterior cingulate cortex is important for the motivation behind attention, but may also be involved in a variety of psychiatric disorders such as depression, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD).[6]

A new area of research within the dorsolateral frontal cortices revolves around "intuition." The frontal lobes can communicate with the limbic system and association cortex. In turn, this emotional influence associated with abstract decision to create more efficient or “intuitive” decision in a short span of time.[7]

Etiology

The cause of frontal lobe disorders includes an array of diseases ranging from closed head trauma (that may cause orbitofrontal cortex damage) to cerebrovascular disease, tumors compressing the frontal lobe, and neurodegenerative disease. Other causes include epilepsy with frontal lobe foci, HIV, multiple sclerosis, and early onset dementia.

Epidemiology

The epidemiology of the frontal lobe syndrome depends on the underlying cause. However, recent studies have suggested that neurodegenerative causes of frontal lobe syndrome may be under-reported.  A previous study in Japan found that there were at least 12,000 FTLD patients, implying that the disease is not as rare as initially thought [8]

Pathophysiology

Based on animal and human studies with frontal lobe lesions, there has been added emphasis on lesions involving the dorsolateral convexity and ventromedial orbitofrontal cortex. Both lesions affect behavior however in different ways. As discussed prior, dorsolateral lesions may cause apathetic and abulic states. In contrast, ventromedial orbitofrontal lesions cause impulsive unrestrained behavior and possibly dangerous decisions. Usually, bilateral lesions produce more significant deficits. There has also been a distinction made between left and right frontal lesions. Left lesions are associated with depression-like symptoms, and right-sided lesions are associated with mania. However, frontal lobe syndrome comprises a variety of behaviors that do not fit into hard and fast rules.

Histopathology

Frontal lobe syndrome due to neurodegenerative disorders is usually caused by 2 main histopathologies: alpha-synuclein and tau protein. Tauopathies that impair the frontal lobes include frontotemporal dementia, chronic traumatic encephalopathy, supranuclear palsy, corticobasal degeneration (CBD), and advanced Alzheimer disease. If tau is hyperphosphorylated, the protein dissociates from microtubules and creates aggregates that are insoluble.[9] The Braak stages classify the degree to which neurofibrillary tangles exist. In contrast, alpha-synuclein is associated with multiple system atrophy, Parkinson disease, and diffuse Lewy body dementia.

History and Physical

The most important element in testing patients with frontal lobe impairment is to perform a thorough neurologic exam. History should also be obtained from family and close contacts to get a “real idea” of how the patient lives. During the exam, it is important to note for behavioral changes such as abulia, inappropriate jocularity (Witzelsucht), insight impairment, confabulation, utilization behavior and environmental dependency (i.e., patients putting on glasses that are not theirs), perseveration, persistence, spontaneous frontal release signs, and incontinence. A mental status exam should be completed to evaluate attention (digit span forward and backward, months forward and backward), memory, perseveration and set shifting ability (Luria alternating sequencing, Trails B, Wisconsin card sorting test), ability to suppress inappropriate response (auditory, visual go-no-go tasks, Stroop testing), word generation (FAS word generation), abstract reasoning, judgement, language, and testing for hemineglect. Other exams include olfaction, optokinetic nystagmus testing (with lesions contralateral to the decreased fast phase), hemiparesis or upper motor neuron signs, motor impersistence, gegenhalten (inability to relax muscles for testing of passive range of motion), primitive reflexes, frontal magnetic gait disturbance, and skull shape to suggest a frontal meningioma. However, during the exam, it is important to note if the patient was subject to past abuse, recent trauma or psychiatric stress.

Evaluation

Before a diagnosis of a frontal lobe syndrome, it is important to rule out other causes that may cause cognitive impairment, for example, B12, thyroid function, and syphilis serology if applicable. In regards to imaging, MRI may be done to evaluate for atrophy, hematomas, vascular and microvascular pathology. Although not as specific or sensitive, CT may be done to rule out acute bleeds or hydrocephalus. If there is clinical suspicion for frontotemporal dementia (FTD), neurologists may consider a deoxyglucose PET scan showing decreased activity in the frontal lobe with sparing of the temporal-parietal areas.[10]

Treatment / Management

Treatment depends on the type of pathology present. For some types of dementia, such as Lewy body, acetylcholinesterase inhibitors have been proven beneficial. In contrast, acetylcholinesterase inhibitors in FTD have not been proven helpful.[11] Nonmedical treatments include physical and occupational therapy, especially in diseases such as frontotemporal dementia. Speech therapy may also be helpful for symptoms like aphasia, apraxia, and dysarthria. Pimavanserin, a selective serotonin 5-HT2A inverse agonist, has been suggested as a new therapy for synuclein-associated psychosis.[12] Furthermore, as executive functioning decline, it is imperative to provide general support at home such as a caretaker.

Differential Diagnosis

Differentials include etiologies that would also affect the frontal lobe such as head trauma, vascular events, primary brain malignancies, abscess, frontal lobe seizures, FTD and developmental abnormalities. More systemic processes include toxic/metabolic disorders, hydrocephalus, Binswanger’s encephalopathy, diffuse anoxic injury, demyelination disorders or advanced Alzheimer disease. Finally, psychiatric causes may also be considered such as the negative symptoms of schizophrenia, depression, Parkinson disease, Huntington disease, or cerebellar lesions.

Prognosis

The prognosis of frontal lobe syndrome depends on the underlying cause. However, for neurodegenerative diseases, there is no cure.

Pearls and Other Issues

Frontal lobe syndrome is due to a broad array of pathologies ranging from trauma to neurodegenerative diseases. The most important clinical feature is the dramatic change in cognitive function such as executive processing, language, attention, and behavior.

Enhancing Healthcare Team Outcomes

A neuropsychologist consult should be done to test the baseline cognitive function better and to create a cognitive treatment plan. Unfortunately, medications for frontal lobe syndrome are mainly aimed to treat symptomatically. During hospitalizations, care should be given to providing a safe and secure environment. Given the complexity and variability within frontal lobe syndrome, cases require an interprofessional team involving nurses, therapists, physicians, and social workers. It is important to plan for a family meeting to discuss end-of-life care should patient no longer have the capacity to make decisions. Non-medical treatments include physical and occupational therapy, especially in diseases such as frontotemporal dementia. Speech therapy may also be helpful for symptoms like aphasia, apraxia, and dysarthria.


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Frontal Lobe Syndrome - Questions

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Somatagnosia is the inability to do which of the following?



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What part of the brain is responsible for social inhibition?



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A patient has a large frontal lobe glioma. Which of the following statements is incorrect about frontal lobe lesions?



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Which of the following is characterized by poor executive function with preservation of language and memory functions?



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Which of the following shows early orbitomedial cortex atrophy?



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A lesion in which part of the brain is associated with urinary incontinence?



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From the image shown, a lesion in which area is associated with gait disturbances?



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A 22-year-old man with a previous head injury from a motor vehicle accident has become very distractible and unmotivated. He cannot seem to concentrate long enough to answer questions directly and appears to repeat the questions. What brain region has been damaged?



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Which is not characteristic of a frontal lobe lesion?



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Which treatment should be avoided in patients with dementia with Lewy bodies?



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A 20-year-old female presents to the clinic with her boyfriend for failure to get to work on time. She consistently turns the light switch 12 times on and off before she can leave the house. She cannot leave the house without performing the task, as she feels “off and in danger.” The physical exam is unremarkable. Which area of the brain is most likely affected?



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A 66-year-old male presents to the clinic with his wife for worsening behavior. Close to the time he retired about a year ago, the patient had trouble organizing his files. Initially, the patient was thought to be depressed, leading to his eventual retirement. However, his behavior continued to become disorganized, and his wife complains that he has become hypersexual and has begun making crude remarks at social engagements. The patient does not realize that his actions are offensive. The physical exam is unremarkable. What is the most likely diagnosis?



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A 70-year-old female presents for agitation. At the moment, she cannot tell you the year or where she is. Her medical history is pertinent for multiple sclerosis with urinary incontinence for which she takes oxybutynin. Two days ago she had worsening behavioral symptoms. According to her daughter, she began seeing her deceased husband at various points of the day. However, there are episodes where she is cognitively intact and exhibits insight into having episodes where she “does not feel like herself.” What is the best next step?



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Frontal Lobe Syndrome - References

References

Szczepanski SM,Knight RT, Insights into human behavior from lesions to the prefrontal cortex. Neuron. 2014 Sep 3     [PubMed]
McCrea SM, Intuition, insight, and the right hemisphere: Emergence of higher sociocognitive functions. Psychology research and behavior management. 2010     [PubMed]
Tranel D, "Acquired sociopathy": the development of sociopathic behavior following focal brain damage. Progress in experimental personality & psychopathology research. 1994     [PubMed]
Damasio H,Grabowski T,Frank R,Galaburda AM,Damasio AR, The return of Phineas Gage: clues about the brain from the skull of a famous patient. Science (New York, N.Y.). 1994 May 20     [PubMed]
Yücel M,Wood SJ,Fornito A,Riffkin J,Velakoulis D,Pantelis C, Anterior cingulate dysfunction: implications for psychiatric disorders? Journal of psychiatry     [PubMed]
Daffner KR,Mesulam MM,Holcomb PJ,Calvo V,Acar D,Chabrerie A,Kikinis R,Jolesz FA,Rentz DM,Scinto LF, Disruption of attention to novel events after frontal lobe injury in humans. Journal of neurology, neurosurgery, and psychiatry. 2000 Jan     [PubMed]
Kerchner GA,Tartaglia MC,Boxer A, Abhorring the vacuum: use of Alzheimer’s disease medications in frontotemporal dementia. Expert review of neurotherapeutics. 2011 May     [PubMed]
Cummings J,Isaacson S,Mills R,Williams H,Chi-Burris K,Corbett A,Dhall R,Ballard C, Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet (London, England). 2014 Feb 8     [PubMed]
Guo T,Noble W,Hanger DP, Roles of tau protein in health and disease. Acta neuropathologica. 2017 May     [PubMed]
Bonelli RM,Cummings JL, Frontal-subcortical circuitry and behavior. Dialogues in clinical neuroscience. 2007     [PubMed]
Ismail Z,Nguyen MQ,Fischer CE,Schweizer TA,Mulsant BH, Neuroimaging of delusions in Alzheimer's disease. Psychiatry research. 2012 May 31     [PubMed]
Wada-Isoe K,Ito S,Adachi T,Yamawaki M,Nakashita S,Kusumi M,Hiroe Y,Takada T,Watanabe K,Hikasa C,Nakashima K, Epidemiological survey of frontotemporal lobar degeneration in tottori prefecture, Japan. Dementia and geriatric cognitive disorders extra. 2012 Jan     [PubMed]

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