Frontal Lobe Syndromes Clinical Presentation

The examiner must obtain a history from an informant who knows the patient well. One of the seeming paradoxes of frontal lobe dysfunction is that informants may complain about the patient's "inability to do anything," yet on at least cursory mental status testing, the patient appears normal or only mildly impaired. This dissociation should be a clue that frontal lobe dysfunction may be present. Symptoms of possible frontal lobe dysfunction that should be probed include change in performance at work and changes organizing and executing difficult tasks such as holiday dinners or travel itineraries. ^[3] The examiner should inquire about the following changes:

• Appropriateness of behavior: Does the patient say things that he or she would never have said before, such as "You are so fat" or "That is a really ugly dress"?

• Patient's table manners: Does the patient now take food and start eating before everyone else, or take food from other people's plates without asking?

• Patient's empathy and ability to infer the mental state of others: This kind of dysfunction often leads to inappropriate behavior.

• Possible apathy: Does the patient care less about hobbies, family members, and finances than previously?

• An increase or decrease in the patient's sexuality or in his or her judgment about possible liaisons.

In addition to these data, the examiner should obtain careful developmental, head trauma, and social histories, including educational and personal attainments. The examiner should also probe about possible substance abuse, whether the patient was a victim of past abuse (physical, sexual, or psychiatric) and about major psychiatric stressor (eg, deaths of friends or family, divorce or separation, job loss or financial reversals). Indeed, a detailed past psychiatric history is required.

Dysfunction of parts of the frontal lobe is sometimes associated with aphasia or severe impairment of attention and can make formal neuropsychologic testing or neurobehavioral evaluation problematic.

Many commonly used brief mental state tests, including the Mini-Mental State Examination, are not designed to test frontal lobe function—they are insensitive and not specific to frontal lobe dysfunction. A person with a Mini-Mental State score of 26 from early Alzheimer disease may have relatively preserved frontal lobe function, yet a patient with Pick disease with a similar score may have profound frontal lobe dysfunction. Two validated bedside tools that extend the cognitive screen to the frontal lobes are the Frontal Assessment Battery (FAB) ^[4] and the Montreal Cognitive Assessment (MoCA). ^[5] These instruments may be helpful for bedside evaluation of frontal lobe function.

FAB was shown to be sensitive to frontal lobe damage of the right hemisphere in stroke patients. The findings indicated that several FAB scores (including composite and item scores) provided valid measures of right hemispheric lateral frontal lobe dysfunction, specifically of focal lesions near the anterior insula, in the right middle frontal gyrus, and in the right inferior frontal gyrus. ^[6]

Most neurologists and psychiatrists are familiar with the general principles of evaluating frontal lobe function but a careful detailed evaluation usually requires consultation with a neuropsychologist or cognitive (behavioral) neurologist. Tests relatively sensitive to frontal lobe dysfunction include the following:

• Go/No-Go task: Ask the patient to hold up one finger if the examiner holds up two, and two fingers if the examiner holds up one. Test the patient to ensure his or her understanding of the task. Perform 10 trials. A failure to respond correctly (ie, echopraxia) suggests a lack of normal response inhibition.

• Antisaccade task: After checking eye movements and visual fields, ask the patient to move his or her eyes contralateral to the stimulus (usually a wiggling finger). Therefore, if the left hand wiggles, the patient's eyes should move approximately an equal distance to the right. A failure in the task (visual grasp) may reflect dysfunction in the dorsolateral prefrontal cortex or a lesion interrupting the pathway between this frontal region and the superior colliculus. ^[7]

• Trail-making test (TMT): This test is widely used as a diagnostic tool for eliciting shifts between cognitive sets. ^[8] The TMT contains two parts. In part A (TMTA), subjects must connect 25 numbered circles, and in part B (TMTB), numbers (1-13) and letters (A-M) must be connected in alternating progression, from 1-A to M-13. Total score is the time in seconds spent to complete each part. TMT requires cognitive flexibility generated through activity in the dorsolateral and medial prefrontal cortices. ^[9]

• Lexical fluency (word generation, Thurstone test): Ask the patient to generate as many words as possible beginning with the letter F in one minute. No proper names or derivatives are allowed. A normal score for a native English speaker with at least a high school education is at least 8 words. Note that semantic category fluency tasks (eg, naming as many animals or fruits in a minute as possible) localize to the temporal not frontal lobes. ^[4] Therefore, such tests are not as useful as the letter fluency task for testing frontal lobe dysfunction. Design fluency (how many designs with four lines) has been suggested as an alternative for aphasic patients. Although the lexical fluency test has relatively poor localizing value, marked impairment is lateralizing to the left frontal lobe. ^[10]

• Attention and concentration test: Intact attention and concentration is the foundation on which all other cognitive tests are based. A patient who does not attend normally cannot be tested accurately for cognitive dysfunction. Serial 7s (ie, serial subtraction of 7 from 100 to 65) has been proposed as a measure of attention and concentration. Spelling the word WORLD backwards is commonly used as a substitute for patients who cannot perform the serial 7s. Digit span is also used to measure attention and concentration. A normal span is 6-7 digits forward and 4-5 backward. An abnormal digit span is the most common neuropsychologic deficit in patients with head injury. Attention has a poor localizing value as it may represent diffuse bihemispheric involvement.

• Alternating sequences task: Ask the patient to copy a segment with alternating M s and N s. Perseveration may occur in patients with frontal lobe lesions. Luria's three-step motor program is a sequential performance of three movements, usually the fist-edge–palm test, which is making a fist, laying the hand on edge, and laying the palm of the hand down on the table. Consider perseveration or failure to perform sequential movements an abnormal response.

• The applause test is also a manifestation of perseveration. Patients are asked to clap three times after demonstration by the examiner. Abnormal outcome consists of clapping four or more times (positive applause sign). This test has been felt highly specific for parkinsonian disorders with frontal involvement. ^[11]

• Among the bedside screening tests, the FAB assesses conceptualization (category responses, such as "in what way are a banana and an orange are alike?"), lexical fluency, programming or motor series (Luria), sensitivity to interference (conflicting instructions, such as "tap twice when I tap once"), inhibitory control (Go/No-Go), and environmental autonomy (prehension behavior, such as "do not take my hands"). For MoCA, from the eight domains evaluated, aspects of executive functions are probed using an alternation task adapted from the Trail-making B task, a phonemic fluency task, and a two-item verbal abstraction task.

• Tests for nonspecific cognitive deficits: Nonspecific cognitive deficits may be found in patients with frontal lesions. The deficits described below are not specific to the frontal lobe and may also occur in nonfrontal lesions. General bedside and neuropsychological testing for these deficits is described below.

  • Aphasia: Aphasia may result from lesions in and around the Broca area (see Aphasia).

    • Classic Broca-type aphasia consists of nonfluent speech, grammatical errors, inability to repeat and to name objects and verbs, and deep dyslexia.

    • Aphasia can be assessed at the bedside by asking patients to name and repeat both common and low-frequency words (eg, pen and watch are considered easy, but clip, lens, and hammock are considered difficult). The naming items on the National Institutes of Health Stroke Scale (NIHSS) laminated cards sold by the American Academy of Neurology (AAN) contain six items of moderate difficulty. Repetition should include a sentence with functor words. "No ifs, ands, or buts" is commonly applied. Assess reading, writing, and spontaneous speech. Deep dyslexia and spelling disorders are extremely common in patients with Broca aphasia.

  • Praxis

    • As discussed in Apraxia and Related Syndromes, the engram for skilled limb movements resides in the left inferior parietal lobule in most right-handed people, but the engrams are translated into motor programs by the premotor cortices. Therefore, left frontal lesions, especially near supplementary motor and premotor cortices, can cause limb apraxia.

    • Therefore, patients with frontal lesions can be apraxic for skilled limb movements without losing the knowledge or understanding of the movement. Patients can also be apraxic because of supplementary motor area lesions and convexity lesions, in addition to parietal lesions. Asking the patient to pantomime the use of real tools (eg, scissors, bread knife, hammer, screwdriver) can test praxis.

    • Buccofacial apraxia occurs when patients cannot perform movements with the mouth or lips and localizes separately near the Broca area.

    • Callosal apraxia also may occur with anterior cerebral artery strokes, causing unilateral left-limb apraxia. A curious finding is that callosal apraxia is uncommon after surgical callosotomy but relatively common after strokes of the anterior cerebral artery, which also affect the gyri adjacent to the corpus callosum.

  • Neglect: Neglect is most common after lesions of the right hemisphere involving either the right parietal lobe or the right frontal lobe. Other areas, including the thalamus and the basal ganglia, may also be implicated. Patients with right brain lesions typically neglect the left hemispace. Neglect can be further fractionated into motor and sensory components, extinction, anosognosia (denial of illness), and anosodiaphoria (minimization of illness).

  • Neglect can be tested at the bedside by asking the patient to draw or read. Patients may neglect the left half of the drawing or leave off the left half of words (neglect dyslexia). Cancellation tasks require that the patient cancel or cross out all the letter A s, circles, or some other element mixed with others on a page. Patients with neglect may omit cancelling the targets on the left half of the page. Line bisection tests require the patient to bisect a line of sufficient length (usually 12 inches or more). Patients with neglect may bisect significantly to the right of midline.

  • Constructional apraxia: This refers to the inability to draw. On the Mini-Mental State Examination, subjects are asked to draw interlocking pentagons. Complex figures can be taken from the Wechsler Adult Intelligence Scale (WAIS) or the Rey Complex Figure Test. Constructional apraxia localizes to the right hemisphere or to the frontal lobes.

  • Judgment, insight, and social appropriateness: No good tests exist for these functions other than observation. Patients can score highly on the WAIS or other cognitive tests and still be unable to behave appropriately. Acquired sociopathy can occur with individuals with orbitofrontal cortex injuries who may score highly on all cognitive measures and yet are unable to hold a job, make and maintain long-term personal relationships, and exercise judgment.

  • Memory deficits: Patients with frontal-lobe injuries, especially orbitofrontal injuries, may have deficits of declarative memory or memory for temporal order of events. In 1935, Jacobsen demonstrated impairments in monkeys on delayed response tasks.

  • Lack of originality, inattentiveness, and inappropriate emotional reactions: Some patients with traumatic lesions of the frontal lobes have these qualities. Patients cannot plan, initiate, organize, or form and maintain personal relationships. They lack insight and remain dependent on caregivers despite normal intellect, as measured conventionally. Witzelsucht, a term meaning facetiousness, and moria (a form of euphoria) or lack of concern may appear. Patients undergo personality changes. A famous 19th-century patient named Phineas Gage was injured in the head with a tamping iron, and his friends described a personality change after the injury, saying, "Gage was not Gage." Many such patients have been described, and some are characterized as pseudopsychopaths.

  • Frontal release responses: Frontal release responses, including suck, grasp, snout, and groping reflexes, may be present, as may paratonic rigidity and abnormal gaze. Although these are not cognitive signs of dysfunction, they certainly help in localization and diagnosis.

  • Utilization behavior: This behavior includes using, touching, or playing with an object that most people would consider inappropriate and may be a sign of frontal lobe dysfunction. An example would be a patient taking a physician’s stethoscope off his desk and listening to his heart while the physician is sitting and talking with him.

  • Alien hand syndrome: This occurs when a patient’s hand assumes complex positions that are not under the patient’s volitional control and may also be a sign of frontal systems dysfunction.

• Gait impairment: A relatively upright posture in the setting of short-stride, hesitant, slightly widened-base gait are characteristic of frontal lobe disorders. Some patients, even when helped to stand up, cannot begin walking (ignition apraxia); others have poor balance with risk of falling from the slightest shove or surface irregularity. Frontal gait is common in advanced Alzheimer disease, some vascular dementias, and normal pressure hydrocephalus. This is sometimes referred to as Bruns apraxia, and is found in patients with bilateral frontal lobe disorders. 

• Incontinence: Dysfunction of the posterior superior frontal gyri and anterior parts of the cingulate gyrus can lead to incontinence of urine and stool. Patients frequently have no warning of the need to urinate or defecate, and are surprised and embarrassed when they find they have soiled themselves.

The manifestations of a frontal lobe syndrome in any patient depend on many factors, including baseline intelligence and education, site of the lesions, whether the lesions developed slowly or rapidly, age, possibly sex, and function of nonfrontal brain regions. Causes of frontal lobe dysfunction include mental retardation, cerebrovascular disease, head trauma, brain tumors, brain infections, neurodegenerative diseases including multiple sclerosis, and normal pressure hydrocephalus.

Cerebrovascular disease

The anterior cerebral artery supplies the medial surface of the brain, including the ventromedial frontal lobe, the cingulum, the premotor cortex, and the motor strip. Bilateral anterior cerebral artery infarct is associated with a syndrome of quadriparesis (legs worse than arms) and akinetic mutism.

Occlusion of the artery of Huebner may cause infarction of the head of the caudate nucleus and may result in an agitated confusional state that with time evolves to akinesia, abulia, and mutism, along with personality changes. Language may also be affected.

The anterior branches of the upper division of the middle cerebral artery supply parts of the lateral prefrontal and frontal cortex. Infarction of these arteries may be characterized by planning deficits, impairment of working memories, and apathy as well as weakness of the contralateral face and arm.

Borderzone infarctions between the distribution of the anterior and middle cerebral arteries are characterized by wedge-shaped lesions between the superior and middle frontal gyri and may result in the man-in-the-barrel syndrome with proximal weakness at the shoulder and hip.

Lacunar infarcts that occur in the deep white matter of the frontal lobe, caudate, or putamen may cause dysfunction of frontostriatal circuits.

Some patients with aneurysms and/or hemorrhage of the anterior communicating artery develop infarctions in the basal forebrain. In addition to the akinesia and personality changes already described, patients may develop a striking confabulatory amnesia that is severe and permanent and that resembles Wernicke-Korsakoff syndrome. Mild anomia may also be present. Finally, a syndrome of affective (as opposed to apathetic) depression may occur after strokes affecting predominantly the left frontal lobe. ^[12]

Tumors

A classic presentation of frontal lobe dysfunction is an olfactory groove meningioma characterized by anosmia, loss of inhibition, memory impairment, headaches, and visual symptoms. The frontal lobes are also common sites for primary and metastatic brain tumors.

Traumatic lesions

Closed head injuries are often associated with unilateral or bilateral contusions of the orbitofrontal cortex. Some patients recover completely and others sustain lifelong impairments. The orbitofrontal cortex is susceptible to contrecoup injury when the accelerating brain strikes against bony prominences on the nonaccelerating surface of the anterior cranial fossa.

Prefrontal lobotomies were performed on some patients in the late 1940s and early 1950s with schizophrenia or other severe psychiatric illnesses. In these procedures, fibers connecting the frontal lobe with the basal ganglia were cut. Although some claimed that such patients performed normally on neuropsychological tests, studies were incomplete and lacked appropriate tests sensitive to frontal lobe dysfunction. Many patients performed normally on selected neuropsychological tests but were still unable to function independently.

Other structural causes of frontal lobe dysfunction

Hydrocephalus of any cause may be associated with frontal lobe dysfunction due to increased intracranial pressure and/or stretching of frontostriatal pathways. Normal pressure hydrocephalus (NPH) has received substantial attention as a reversible cause of dementia. Unfortunately, not all patients who seem to meet criteria for NPH are helped with surgery. Core features of NPH are gait apraxia, urinary incontinence, and frontal-predominant cognitive impairment.

Tourette syndrome, a tic disorder associated with prominent behavioral disorders such as obsessive-compulsive disorder, is associated with alterations in frontal lobe regions connected to the striatum. In particular, prefrontal areas and anterior cingulate gyrus are reduced in volume compared with age- and sex-matched healthy individuals. ^{[5, 13]} In this condition, tics are worse when the volume of the orbitofrontal and right cingulate gyrus is less.

Frontotemporal lobar degenerations (FTLD)

These disorders include at least 4 clinically distinguishable neurocognitive syndromes based on the location of the pathologic burden: (1) behavioral variant of frontotemporal dementia (bvFTD), (2) primary progressive aphasia (PPA), also known as progressive nonfluent aphasia (PNFA), (3) logopenic progressive aphasia (LPA) and (4) semantic dementia (SD), also known as fluent PPA. These disorders are all slowly progressive neurodegenerative disorders. ^[14] The bvFTD and PNFA are the only FTLDs truly affecting the frontal lobes. Although LPA and SD are considered within the spectrum of FTLD, they result from primary involvement of the parietal and temporal regions, respectively.

• FTD, the behavioral variant of FTLD, results from bilateral frontal atrophy and causes a dementia syndrome with changes in personality in the context of relative preservation of memory and language (economical speech) but impairments in abstraction, attention, problem solving, and planning. Echolalia, perseveration, and stereotypical use of words may arise. Three clinical FTD phenotypes may be defined based on the distribution of regional atrophy:

  • Orbitobasal or pseudopsychopathic FTD causes disinhibition and irritability.

  • Mediofrontal (anterior cingulate) FTD leads to mutism and apathy.

  • Dorsolateral prefrontal or pseudodepressive FTD, probably the most common variant, is recognized by apathy, psychomotor retardation, and executive dysfunction, expressed as reduced learning and retrieval with decreased problem solving and set shifting.

• PPA or PNFA, due to left frontal and temporal atrophy, causes nonfluent and nonrepetitive speech with word-finding difficulty and agrammatism (syntactic aphasia), progressing to stuttering, phonemic paraphasias, anomia, and mutism.

• LPA due to atrophy in the posterior portion of the left superior and middle temporal gyri and inferior parietal lobe results in slow speech rate with long word-finding pauses. Grammar and articulation are preserved, although phonological paraphasias can be present. Repetition and comprehension were impaired for sentences but preserved for single words, and naming is moderately affected. ^[15]

• SD or fluent PPA, due to left anterolateral temporal atrophy with relative sparing of hippocampus (right-sided involvement causes progressive prosopagnosia), results in a syntactically fluent but empty speech, semantic paraphasias, and shrinking vocabulary (poor word retrieval and semantics).

Infectious causes of frontal lobe dysfunction

HIV frequently affects basal ganglia, hippocampus, and the deep white matter of the frontal lobe. The spectrum of cognitive impairment in HIV ranges from no impairment to HIV-dementia. Abscesses in the frontal lobe can also impair frontal lobe function.