Frontal Lobe Syndrome

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 [9]. 

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's disease. If tau is hyperphosphorylated, the protein dissociates from microtubules and creates aggregates that are insoluble.[10] The Braak stages classify the degree to which neurofibrillary tangles exist. In contrast, alpha-synuclein is associated with multiple system atrophy, Parkinson's 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, judgment, 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 diagnosing 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.[11]

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.[12] 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.[13] Furthermore, as executive functioning declines, it is imperative to provide general support at home such as a caretaker.(A1)

Differential Diagnosis

Differentials include etiologies that would also affect the frontal lobe such as:

• Head trauma
• Cerebrovascular accident
• Cerebral malignancies
• Frontal lobe seizures
• Hydrocephalus
• Binswanger’s encephalopathy
• Anoxic injury
• Alzheimer's disease
• Schizophrenia
• Parkinson's disease
• Huntington disease

Prognosis

The prognosis of frontal lobe syndrome depends on the underlying cause. For reversible and treatable causes such as infections or resectable tumors, the prognosis is more favorable than progressive neurogenerative disorders such as frontotemporal dementia. In the latter cases, treatment is based on symptom control and patients will eventually succumb to the disease. 

Complications

Complications of frontal lobe syndromes are cause specific. Progressive neurodegenerative disorders have social and behavioral complications requiring multifaceted support services for the patients and their families.