During brain surgery, the superior portion of the postcentral gyrus of a patient is stimulated

Insular Lobe

The insular lobe, also known as the insula, is concealed deep inside the sylvian fissure and is covered by the frontal, central, parietal, and temporal lobes. It is traditionally described as a pyramid with a triangular base, with an anterior surface (covered by the frontoorbital operculum), a superior surface covered by the frontoparietal operculum, and an inferior surface covered by the temporal operculum (Wen et al., 1999, Wen et al., 2009)

The insular lobe is divided by the central sulcus (obliquely arranged, like the central sulcus of the central lobe) in an anterior portion formed by small insular gyri and a posterior portion of long insular gyri parallel to the central sulcus. On the surface, the central sulcus of the insular lobe is covered by the subcentral gyrus (which connects the precentral and postcentral gyri). As a rule, three insular gyri originating at the point defining the apex of the pyramid of the insular lobe comprise the anterosuperior portion. The so-called transverse and accessory gyri, located on the anteroinferior face of the pyramid, comprise what is known as the insular pole, which is connected to the posterior and medial orbital gyri. The insular apex protrudes under the anterior sylvian point, which in turn is defined by the tip of the so-called pars triangularis of the frontal operculum. The smaller surface of the posterior portion comprises two large oblique gyri parallel to the central sulcus, known as the anterior and posterior long gyri of the insula (Fig. 1.9) (Ribas and de Oliveira, Mar 2007, Türe et al., 1999, Wen et al., 2009).

The insular lobe is surrounded by the circular sulcus of Reil, which is also divided into superior, inferior, and anterior limiting sulci. The superior limiting sulcus forms the transition between the superolateral surface of the insula and the frontoparietal operculum. The superior limiting sulcus continues along the surface as the anterior horizontal ramus of the sylvian fissure. The inferior limiting sulcus defines the transition between the inferolateral surface of the insula and the temporal operculum. Finally, the anterior limiting sulcus of the insular lobe is a deep sulcus between the anterior surface of the insula and the posterobasal surface of the frontal lobe (frontoorbital operculum). The anterior limiting sulcus continues along the surface as the anterior ascending ramus of the sylvian fissure (Fig. 1.9) (Wen et al., 2009).

The surface of the insular lobe forms an envelope for a set of elements that a number of authors refer to as the central core of the brain. This cortical gray matter covers a heterogeneous collection of elements, among which are the thalamus, basal nuclei, and internal capsule. The entire central core is surrounded by the lateral ventricle, which means that the superior limiting sulcus protrudes over the body of the lateral ventricle and the inferior limiting sulcus over the temporal horn. The posterior apex of the circular sulcus, the point of confluence for the superior and inferior limiting sulci of the insula, comprises the sylvian point in the anterior angiographic projection, and is located in proximity to the atrium of the lateral ventricle (Ribas and de Oliveira, Mar 2007, Ribas et al., 2006, Türe et al., 1999).

Motor Dysfunctions

Because the ACA irrigates the paracentral lobule, the classic syndrome of unilateral ACA occlusion is contralateral leg monoplegia, with mild upper extremity involvement, mainly in the shoulder, or leg monoplegia combined with arm ataxia.16,22 Because of the infrequency of ACA infarction, hemiparesis predominating in the leg actually occurs more often after discrete infarcts of the pyramidal tract in the deep cerebral white matter or brainstem, rather than after ACA infarction.23 Some patients have a complete faciobrachiocrural hemiplegia, which causes confusion with MCA infarcts.21 Other motor abnormalities of the arm include a grasp reflex, forced grasping, paratonia, gegenhalten, micrographia, left arm apraxia or the “alien hand,”24 and motor perseveration with the hand.16 Damage to the supplementary motor cortex causes some of the foregoing motor deficits of the hand including underuse and lack of spontaneous movements.16,25 Urinary incontinence may occur after bilateral lesions or large unilateral ACA infarctions.18,20,26

Weakness and Sensory Loss

ACA occlusion causes infarction of the paracentral lobule and, as a result, weakness and sensory loss in the contralateral leg (Fig. 6-4a and Fig. 6-4b).151152153154155156 The deficit is usually greatest distally for the following two reasons: (1) the proximal leg is represented on the primary sensorimotor cortex either superiorly on the medial hemisphere or on the high convexity with, therefore, richer collateral vessels from the MCA and (2) proximal muscles have substantial representation in the ipsilateral hemisphere.157 If infarction extends to the upper convexity, there may be proximal arm weakness or, as is usual with cortical lesions, clumsiness or slowness out of proportion to the actual loss of strength.

Paretic muscles are initially most often flaccid, becoming spastic over days or weeks; at the outset, tendon reflexes may be decreased, normal, or increased.159 (This common early dissociation between tone and tendon reflexes has been attributed to the loss of supraspinal influence on different kinds of muscle spindle afferents, for example, phasic versus tonic.) Babinski's sign may be present.

The sensory modalities most often affected are discriminative (two-point discrimination, localization, stereognosis) and proprioceptive (position sense). Pain and temperature sensation and gross touch are usually only mildly decreased; the patient can tell sharp from dull, but the pinprick does not feel as sharp or as "normal" as on the unaffected side. Vibratory loss is variable. Depending on the posterior extent of the ACA and collaterals from the PCA, sensory loss may be mild or even absent in the presence of marked crural hemiparesis.31 Sensation may be similarly spared when occlusion is not of the ACA or the pericallosal artery but of the paracentral branch.31160161162163

In the acute phase, the head and eyes may be deviated toward the side of the lesion.31164165 Forced grasping and groping of the contralateral hand, whether or not it is weak, follows damage to the posterior superior frontal gyrus.31166167168 Such forced grasping has been considered "a type of limb-kinetic apraxia" and "only one aspect of a total change in behavior toward a compulsive exploration of the environment"169; foot grasping170 can cause the lower limb to seem "glued to the floor"169 on attempted walking. Patients with such findings also display sucking and biting,169“ansaugen” (a movement of the lips and tongue toward stimulation of the skin near the lower lip),167 bradykinesia (or an “absence of movement intention”),31171172 catalepsy,173 and “tonic innervation” (“amorphous movements of a pseudospontaneous character”)31 on attempted voluntary action of the affected arm or leg.170171172 During the first few days after ACA territory infarction, two patients displayed "hyperkinetic motor behaviors" (including head and eye movements, grimacing, chewing, rubbing body parts, rhythmically moving the fingers, and flexing and extending the thigh) on the contralateral, nonparalyzed side.174 It was suggested that such movements (which also occurred contralateral to hemiplegia after MCA territory infarction) signify “an active process induced by disinhibition in order to establish new compensatory pathways.”

Pronounced weakness of the arm and face in the presence of ACA occlusions has been attributed to involvement of Heubner's artery and its supply to the anterior limb and genu of the internal capsule (Fig. 6-5).31155 If the circle of Willis is complete, such proximal thrombosis must extend as far as the ACoA to produce complete hemiplegia, or the contralateral ACA takes over the supply of both medial hemispheres and weakness is limited to the face and arm. Paralysis of the right arm, paresis of the right face, and only slight weakness of the right leg occurred in a man who at autopsy was found to have infarction of the left putamen, caudate, and anterior limb of the internal capsule, plus a “shrunken and occluded artery of Heubner.”31 (The leg weakness was attributed to additional softening in the territories of the ACA's middle and posterior internal frontal branches.)

Later anatomic studies have shown, however, that Heubner's artery supplies only the most anterior striatum and anterior limb of the internal capsule and is, therefore, probably uncommonly the responsible vessel when brachial or facial palsy accompanies ACA occlusion. The more likely possibility in such a situation is involvement of penetrating branches arising from the most proximal ACA and the internal carotid bifurcation, which supply the genu and the anterior part of the internal capsule's posterior limb in addition to the hypothalamus and the rostral thalamus.46 Moreover, caudate infarction can cause contralateral limb bradykinesia, clumsiness, and loss of associated movements mistakenly interpreted as weakness.57 Dysarthria has followed unilateral infarction of either the left or right anterior limb of the internal capsule, and in one report, dysarthria occurred after infarction apparently confined to the caudate nucleus.57 Five patients with unilateral capsular genu infarction had contralateral facial and lingual weakness with dysarthria, three had unilateral mastication-palatal-pharyngeal weakness, and one had unilateral vocal cord paresis; the only limb involvement was mild hand weakness in three patients.175

As previously noted, the ACA territory in some individuals encompasses a considerable portion of the upper cerebral convexity; in such a situation, infarction would include arm and hand representations on the primary motor (and sensory) cortex.71 Conversely, in subjects with a smaller than usual ACA territory, leg weakness can be a consequence of MCA or PCA territory infarction. Of 63 patients in one series with acute stroke and “leg-predominant weakness,” 12 had infarction in the ACA territory, 9 in the MCA territory, 2 in both territories (not "watershed”), 18 in the internal capsule, 10 in the brainstem, and 2 in the thalamus.176 Leg weakness was more lasting when infarction involved the motor cortex than when it involved the premotor cortex or supplementary area and spared the motor cortex.

Of 100 patients reported by Moulin and coworkers177 as having "ataxic hemiparesis" after a first stroke, 4 had infarction of the contralateral ACA territory. Pyramidal weakness was greatest in the leg, with ataxia of the cerebellar type in the ipsilateral arm. Such ataxia has been attributed to involvement of frontopontocerebellar projections and also, on the basis of single-photon emission computed tomography (SPECT) studies, to trans-synaptic dysfunction of the contralateral cerebellum (diaschisis).178179 A problem with the ataxic hemiparesis syndrome—regardless of the lesion's location—is that upper motor neuron lesions, as a rule, produce clumsiness out of proportion to weakness; determining whether the "ataxia" is qualitatively or quantitatively sufficient to label it "cerebellar" can be difficult.

Infarction in the territories of both ACAs causes paraparesis, with or without sensory loss.180 Paraparesis occurs most often as a consequence of bilateral ACA vasospasm after rupture of an ACA or ACoA aneurysm.181 In thrombotic or embolic infarction, paraparesis is especially likely when there is a vascular anomaly, such as a hypoplastic A1 segment or an azygous distal ACA.31119164182183184185 Particularly when symptoms are stutteringly progressive, spinal cord disease may be erroneously suspected.2729186187 Even if weakness is mild or absent, there may be severe gait disturbance, with inability to initiate the first step with either foot, to lift either foot off the ground, or to turn to either side (“slipping clutch syndrome"190).188189 Grasp reflexes of the feet (or hands) are not present in all affected patients, and although some can move their legs freely in the air (e.g., bicycling motions),190 others cannot.188 When severe, such medial prefrontal damage can produce a pronounced immobility of all four limbs, from bradykinesia to catatonic (perseverative) posturing with gegenhalten, sucking, and biting.190 In one such report the patient had unexplained vertical gaze palsy (upward and downward), suggesting midbrain localization.191

The gait disability bears an obvious resemblance to that found with hydrocephalus and with the paraplegia in flexion of degenerative disease that mainly affects the frontal lobes192; in these conditions, the pathophysiology is not understood, and the possible roles of descending frontal and prefrontal fibers193194 or the globus pallidus195 are uncertain. Pulsatile flow in the ACAs is decreased in infantile hydrocephalus,196 and some researchers have suggested that secondary ACA ischemia may be the cause of lower extremity spasticity in hydrocephalic infants and may contribute to the gait disturbance seen in adult normal-pressure hydrocephalus.197

Weakness and Sensory Loss

ACA occlusion causes infarction of the paracentral lobule and, as a result, weakness and sensory loss in the contralateral leg (Fig. 23-4).177–182 The deficit is usually greatest distally for the following two reasons: (1) the proximal leg is represented on the primary sensorimotor cortex either superiorly on the medial hemisphere or on the high convexity with, therefore, richer collateral vessels from the MCA and (2) proximal muscles have substantial representation in the ipsilateral hemisphere.183 If infarction extends to the upper convexity, there may be proximal arm weakness or, as is usual with cortical lesions, clumsiness or slowness out of proportion to the actual loss of strength.

Paretic muscles are initially most often flaccid, becoming spastic over days or weeks; at the outset, tendon reflexes may be decreased, normal, or increased. (This common early dissociation between tone and tendon reflexes has been attributed to the loss of supraspinal influence on different kinds of muscle spindle afferents [e.g., phasic versus tonic].) Babinski's sign may be present.

The sensory modalities most often affected are discriminative (two-point discrimination, localization, stereognosis) and proprioceptive (position sense). Pain and temperature sensation and gross touch are usually only mildly decreased; the patient can tell sharp from dull, but the pinprick does not feel as sharp or as “normal” as on the unaffected side. Vibratory loss is variable. Depending on the posterior extent of the ACA and collaterals from the PCA, sensory loss may be mild or even absent in the presence of marked crural hemiparesis.43 Sensation may be similarly spared when occlusion is not of the ACA or the pericallosal artery but of the paracentral branch.43,184–187 Sensory loss can also occur in the absence of weakness.188,189

In the acute phase, the head and eyes may be deviated toward the side of the lesion.43,190,191 Forced grasping and groping of the contralateral hand, regardless of whether it is weak, follows damage to the posterior superior frontal gyrus.43,192–194 Such forced grasping has been considered “a type of limb-kinetic apraxia” and “only one aspect of a total change in behavior toward a compulsive exploration of the environment”;195 foot grasping196 can cause the lower limb to seem “glued to the floor”195 on attempted walking. Patients with such findings also display sucking and biting,188 “ansaugen” (a movement of the lips and tongue toward stimulation of the skin near the lower lip),193 bradykinesia (or an “absence of movement intention”),43,197,198 catalepsy,199 and “tonic innervation” (“amorphous movements of a pseudospontaneous character”)43 on attempted voluntary action of the affected arm or leg.196–198 During the first few days after ACA territory infarction, two patients displayed “hyperkinetic motor behaviors” (including head and eye movements, grimacing, chewing, rubbing body parts, rhythmically moving the fingers, and flexing and extending the thigh) on the non-paralyzed side.200 It was suggested that such movements (which also occurred contralateral to hemiplegia after MCA territory infarction) signify “an active process induced by disinhibition in order to establish new compensatory pathways.”

The “pusher syndrome”, a disturbed control of upright body posture in which the patient suffers from a severe misperception of his body's orientation in the coronal plane, was described in a patient with a right ACA infarction, severe left hemiparesis, spatial neglect, visual and auditory extinction, and forced contraversive pushing away from the non-paralyzed side.201,202

Pronounced weakness of the arm and face in the presence of ACA occlusions has been attributed to involvement of Heubner's artery and its supply to the anterior limb and genu of the internal capsule (Fig. 23-5).43,203 If the circle of Willis is complete, such proximal thrombosis must extend as far as the ACoA to produce complete hemiplegia, or the contralateral ACA takes over the supply of both medial hemispheres and weakness is limited to the face and arm. Paralysis of the right arm, paresis of the right face, and only slight weakness of the right leg occurred in a man who at autopsy was found to have infarction of the left putamen, caudate, and anterior limb of the internal capsule, plus a “shrunken and occluded artery of Heubner.”43 (The leg weakness was attributed to additional softening in the territories of the ACA's middle and posterior internal frontal branches.) “Capsular warning syndrome”, with recurrent attacks of left face, arm, and leg weakness followed by fixed hemiplegia, was attributed to atherosclerotic stenosis of Heubner's artery, verified angiographically.204

Later anatomic studies have shown, however, that Heub­ner's artery supplies only the most anterior striatum and anterior limb of the internal capsule and is, therefore, probably uncommonly the responsible vessel when brachial or facial palsy accompanies ACA occlusion. The more likely possibility in such a situation is involvement of penetrating branches arising from the most proximal ACA and the internal carotid bifurcation, which supply the genu and the anterior part of the internal capsule's posterior limb in addition to the hypothalamus and the rostral thalamus.54 Moreover, caudate infarction can cause contralateral limb bradykinesia, clumsiness, and loss of associated movements mistakenly interpreted as weakness.65 Dysarthria has followed unilateral infarction of either the left or right anterior limb of the internal capsule, and in one report, dysarthria occurred after infarction apparently confined to the caudate nucleus.65 Five patients with unilateral capsular genu infarction had contralateral facial and lingual weakness with dysarthria, three had unilateral mastication-palatal-pharyngeal weakness, and one had unilateral vocal cord paresis; the only limb involvement was mild hand weakness in three patients.205

As previously noted, the ACA territory in some individuals encompasses a considerable portion of the upper cerebral convexity; in such a situation, infarction would include arm and hand representations on the primary motor (and sensory) cortex.79,206 Conversely, in subjects with a smaller than usual ACA territory, leg weakness can be a consequence of MCA or PCA territory infarction. Of 63 patients in one series with acute stroke and “leg-predominant weakness,” infarction occurred in 12 in the ACA territory, in nine in the MCA territory, in two in both territories (not “watershed”), in 18 in the internal capsule, in ten in the brainstem, and in two in the thalamus.207 Leg weakness was more lasting when infarction involved the motor cortex than when it involved the premotor cortex or supplementary area and spared the motor cortex.

Of 36 consecutive patients with isolated pericallosal artery territory infarction, 29 had hemiparesis with leg predominance, yet only five had abnormal motor-evoked potential recordings, indicating preserved corticospinal tracts. The weakness was attributed to supplementary motor area (SMA) damage.208

Of 100 patients with “ataxic hemiparesis” after a first stroke, four had infarction of the contralateral ACA territory.209 Pyramidal weakness was greatest in the leg, and ataxia of the cerebellar type was seen in the ipsilateral arm. Such ataxia has been attributed to involvement of frontopontocerebellar projections and also, on the basis of single-photon emission computed tomography (SPECT) studies, to transsynaptic dysfunction of the contralateral cerebellum (diaschisis).210,211 A problem with the ataxic hemiparesis syndrome – regardless of the lesion's location – is that upper motor neuron lesions, as a rule, produce clumsiness out of proportion to weakness; determining whether the “ataxia” is qualitatively or quantitatively sufficient to label it “cerebellar” can be difficult.

The transient ischemic attack syndrome of limb shaking of the leg was described in a woman with an acute infarction on the right corpus callosum and cingulate gyrus secondary to focal stenosis of the right ACA. She had episodic shaking movements of the left leg one to 15 times per day, preceded by a brief sensation of weakness and elicited only when she arose from a sitting position.212

Infarction in the territories of both ACAs causes paraparesis, with or without sensory loss.213 Paraparesis occurs most often as a consequence of bilateral ACA vasospasm after rupture of an ACA or ACoA aneurysm.214,215 In thrombotic or embolic infarction, paraparesis is especially likely when there is a vascular anomaly, such as a hypoplastic A1 segment or an azygous distal ACA.39,133,183,216-222 Particularly when symptoms are stutteringly progressive, spinal cord disease may be erroneously suspected.40,41,223,224 Even if weakness is mild or absent, there may be severe gait disturbance, with inability to initiate the first step with either foot, to lift either foot off the ground, or to turn to either side (“slipping clutch syndrome”).225-227 Grasp reflexes of the feet (or hands) are not present in all affected patients, and although some can move their legs freely in the air (e.g., bicycling motions),227 others cannot.225 When severe, such medial prefrontal damage can produce a pronounced immobility of all four limbs, from bradykinesia to catatonic (perseverative) posturing with gegenhalten, sucking, and biting.227 In one such report the patient had unexplained vertical gaze palsy (upward and downward), suggesting midbrain localization.228

The gait disability bears an obvious resemblance to that found with hydrocephalus and with the paraplegia in flexion of degenerative disease that mainly affects the frontal lobes;229 in these conditions, the pathophysiology is not understood, and the possible roles of descending frontal and prefrontal fibers230,231 or the globus pallidus232 are uncertain. Pulsatile flow in the ACAs is decreased in infantile hydrocephalus,233 and some researchers have suggested that secondary ACA ischemia may be the cause of lower-extremity spasticity in hydrocephalic infants and may contribute to the gait disturbance seen in adult normal-pressure hydrocephalus.234

A man whose anomalous ACAs resulted in bilateral infarction restricted to the supplementary motor areas had what was considered gait apraxia; he had difficulty standing from a chair on command, rolling over in bed, starting or stopping walking, and maintaining stance. There were no elementary motor abnormalities, and the authors considered his disorder a “loss of monitoring of the automatic implementation of gait mechanisms.”235 Drop attacks and right-sided limb-shaking TIAs occurred in a man with left ICA stenosis and a left A1 segment of the ACA supplying both medial frontal lobes; symptoms resolved after endarterectomy.236

Corticobasal Degeneration

Corticobasal degeneration (CBD) is a rare, largely sporadic, and idiopathic degenerative disorder of posterofrontal lobe and paracentral lobule (precentral and postcentral gyri; sometimes unilateral and asymmetrical), basal ganglia, and substantia nigra. Other names of this disorder include corticobasal ganglionic degeneration, corticonigral degeneration, and corticodentatonigral degeneration with neuronal achromasia. CBD is a clinically unique movement disorder that may or may not be accompanied by frontotemporal dementia at late stage. Patients often present in their 60s with asymmetrical involuntary movements (jerks), clumsiness, and stiffness of limbs, followed by dystonic rigidity, akinesia, and myoclonus of the affected limbs. Many patients feel dissociated from the affected limbs (“alien limb”). Pyramidal deficits from upper motor neuron degeneration, aphasia, dysarthria, and dysphagia may appear in late stage with limb contractures. These symptoms are refractory to levodopa treatment, and disease usually lasts 6 to 10 years. On neuroimaging studies and gross examination, brains from patients with CBD show marked, often asymmetrical cortical atrophy of posterior frontal lobe (especially superior frontal gyrus) and superior parietal lobule. The underlying white matter and portion of corpus callosum are often atrophic. The substantia nigra and locus ceruleus are degenerated and depigmented. Microscopically, the affected cortical areas show severe neuronal loss, marked gliosis with neuropil rarefaction (“status spongiosus”) (Fig. 27.8A), and formation of many phosphorylated neurofilament-immunoreactive ballooned neurons (also known as achromatic neurons, achromasic neurons, or Pick cells; Fig. 27.8B) in layers III, V, and VI. Residual large neurons in the degenerated substantia nigra and locus ceruleus contain weakly basophilic, argyrophilic (Fig. 27.8C), and tau-positive corticobasal inclusions similar to globose NFTs seen in AD and PSP. Argyrophilic, tau-positive, ubiquitin-negative, and α-synuclein–negative coiled bodies similar to those seen in PSP are present in gray and white matter. In addition to widespread glial and neuronal cytoplasmic inclusions of various sizes and shapes, tau IHC stain demonstrates “astrocytic plaques” (Fig. 27.8D) in cortical and neostriatal neuropil as ill-defined and annular arrays of short stubby astrocytic processes specific for CBD. Astrocytic plaques can also be demonstrated on some (e.g., Gallyas), but not other (e.g., Bielschowsky) silver stains, and their appearance is distinct from that of the smaller and densely packed tufted astrocytes seen in PSP. The diagnostic yield of a frontal lobe brain biopsy is predictably low, but the detection of astrocytic plaques and glial cytoplasmic inclusions may be diagnostic of CBD in an appropriate clinical context.

Cells of Origin

The cells of origin of the corticospinal tract are located in the precentral gyrus, mainly in its upper two-thirds, and in the paracentral lobule. Brodmann's areas 4 (primary motor cortex) and 6 (nonprimary motor cortex) contribute 80% of the pyramidal tract fibers (see Chapter 27 for diagrammatic and pictorial representation of cortical regions, e.g., Fig. 27). In contrast to other mammals, contribution of corticospinal fibers from the postcentral gyrus is sparse in the human. Corticospinal fibers are not derived exclusively from the large lamina V Betz cells of area 4.

Cuts with the cingulate

The callosal fibers make a bend around the cingulum bundle as they connect mostly analogous parts of the parasagittal brain, that is, SFG to SFG, paracentral lobule to paracentral lobule, etc. This important fact suggests that it is possible to preserve the cingulate system while removing the corpus callosum. This should not be surprising given that we have been safely cutting this for years, and have been entering the frontal horn transcortically for years (which cuts the forceps minor).

It is key to note that anterior callosum tumors are really frontal tumors which involve the callosum, and should be taken out through the middle frontal gyrus, which both addresses the tumor and avoids the DMN and salience systems. This means you usually find the cingulate from its deep surface. In addition to using the cingulate sulcus as a key landmark, intraoperative mapping tells you when you need to deviate laterally to avoid cutting the cingulum bundle on your way to the ventricle. Thus, the cut with the cingulum is a sagittal cut, and the deviations needed to avoid it are movements of this sagittal plane in response to changes in the patient.

I.A.2 Medial Organization

The cortex lining the medial wall of the hemisphere, located directly above the anterior portion of the paracingulate and/or cingulate sulci is divided into the paracentral lobule caudally and the medial frontal gyrus rostrally (Fig. 1). The division between the paracentral and medial frontal gyri is occasionally formed by a vertical sulcus emerging from the cingulate sulcus above the midpoint of the corpus callosum. The primary somatosensory (S1) and primary motor (M1) cortices occupy caudal and rostral portions of the paracentral lobule, respectively. The supplementary motor cortex (M2), presupplementary motor cortex (P-SMA), and prefrontal cortex comprise the caudal to rostral components of the superior frontal gyrus. Bordering the medial frontal gyrus ventrally is the cingulate gyrus and its affiliated subcallosal extension. In a majority of cases, the paracingulate sulcus roughly defines the border between the frontal lobe and the cingulate cortex of the limbic lobe. Ventral to the paracingulate sulcus is the cingulate sulcus. Rarely, an intralimbic sulcus is located ventral to the cingulate sulcus. Rostral (M3) and caudal (M4) cingulate motor cortices are located in the dorsal portion of the cingulate cortex.

Primary Motor Cortex

The PMC is comprised of unimodal idiotypical cortex occupying the posterior part of the precentral gyrus, the anterior bank of the central sulcus, and the anterior part of the paracentral lobule. The region is histologically distinguished by large neurons known as the gigantopyramidal cells of Vladamir A. Betz. BA 4 receives projections from the preMC, the SMC, and multiple parietal regions. Fibers from the PMC descend through the pyramidal tract (about one-third of pyramidal tract neurons originate in PMC) ultimately to synapse on neurons in the brainstem and the anterior horn of the spinal cord. The connectivity and functional activity in this region point to its role in initiation and control of fine movements. PMC neurons fire approximately 60 milliseconds before movement, and fire faster with low levels of muscular force.7 While stimulation studies show that PMC neurons control only contralateral limbs, unilateral stimulation in regions controlling the upper face, soft palate, laryngeal muscles, masticatory muscles, and trunk usually cause bilateral movement. Landmark studies by Penfield in 1950 demonstrated an organization to the PMC representation of movement, with a progression through face, arm, trunk, and legs from inferolateral to medial superior portions of the frontal lobe.8 These studies also showed that larger regions of the PMC are devoted to movement of the face, tongue, and distal musculature than to more proximal muscle groups.

Injury limited to the pyramidal tract and PMC results in a complex set of symptoms. Lesions that cause electrical excitability limited to these regions (seizures) cause focal clonic jerking, the location of which depends on the seizure focus. Seizures can sometimes represent the organization of PMC neurons by progressively involving face, then arm, then leg contralateral to the seizure focus (called a Jacksonian march after Hughlings Jackson, who described the phenomenon in 1868). Lesions such as stroke, trauma, or inflammation can cause severe weakness in early stages, which often evolves over time to become quite mild. The distal musculature tends to be weaker than the proximal, perhaps owing to a proportionally greater cortical representation. Even when weakness is absent, fine finger movements may be impaired, supporting theories that BA 4 is particularly important for fine coordination. In addition to weakness, lesions of the corticospinal tract cause a classic constellation of “upper motor neuron” findings on neurological examination, which include spastic rigidity, meaning a velocity-dependent change in muscle resistance to passive stretch, as well as an increase in stretch reflexes. Abnormal reflexes may become apparent, such as the Babinski sign in which the toes fan up and apart when the bottom of the foot is scratched. The exact constellation of symptoms depends on the location and extent of the cortical lesion.

Hemispheric paracentral periventricular white-matter lesions

The output of the thalamus critical for gait is directed to the areas of the cortex involved in lower-extremity movements. This area of the cortex is the medial frontal region, specifically, the paracentral lobule and the supplementary motor cortex. The fibers reaching this area from the thalamus course through the periventricular white matter. Thus, it is not surprising that lesions here may result in impaired gait. The kind of gait impairment seen most often in these patients corresponds to what has been termed the “cautious gait” (Sudarsky and Tideiksaar, 1997). Because they have poor balance, their steps are shorter, possibly to lessen the single-foot stance portion of the gait cycle. Like patients with thalamic lesions, these individuals may seem to walk rather normally so long as they pay attention to their gait. However, when they engage the “automatic pilot,” and the motor control system for involuntarily movements begins to be relied upon, they tend to fall. Often, patients with a shuffling, unsteady gait at home perform normally at a physician's office: they are successfully engaging the cortical mechanisms of gait to compensate for the impaired subcortical mechanisms. Here, the history, coupled with the neuroimaging findings, can be most helpful (Srikanth et al., 2009).

CT or, preferably, MRI is indicated to study this kind of gait and balance impairment. Beginning with a report in 1989, many studies have confirmed that white-matter abnormalities on CT and MRI correlate with impaired gait unbalance in older people (Masdeu et al., 1989; Baloh et al., 1995; Camicioli et al., 1999). However, white-matter changes on CT or MRI are very frequent in older people (Fig. 48.8). On MRI, some degree of white-matter change is present in about 95% of subjects over the age of 60 and increases with age (de Leeuw et al., 2001; Qiu et al., 2009). Areas in the hemispheric white matter are hypodense on CT and markedly hyperintense on T2-weighted images and FLAIR, and hypointense on T1-weighted images (Fig. 48.8). However, high-intensity areas on T2-weighted MRI are often undetected on CT. On T2-weighted MR images, it may be difficult to differentiate tissue damage from increased water content due to dilation of perivascular spaces with normal aging because both have increased intensity values (Kirkpatrick and Hayman, 1987). For this reason, in older persons it seems preferable to quantify lesions visible on T1-weighted images or CT as indicators of true white-matter damage. However there are few data available in this age group exploring the functional significance of white-matter changes visible only on T2-weighted images versus those visible on both T2- and T1-weighted images.

In multiple sclerosis, and therefore in a younger age group, it is known that T1 lesion volume correlates better than T2 volume with hemispheric dysfunction (Comi et al., 2000). T1 mapping, which determines tissue-specific T1 relaxation times, has been used recently to correlate postmortem changes (Vrenken et al., 2006; Gouw et al., 2008a). It may reflect pathologic processes related to intraparenchymal changes in water content such as edema, widening of the extracellular space, subtle blood–brain barrier leakage, or glial proliferation (Vrenken et al., 2006; Gouw et al., 2008a). MRI is more helpful than CT to identify amyloid angiopathy as the cause of white-matter disease (Gray et al., 1985; Mead et al., 2000). In addition to white-matter changes, amyloid angiopathy results in subcortical hemorrhages, easily seen on CT when they are large, but not when they are small, so-called microhemorrhages; these are best seen on gradient-echo or susceptibility-weighted MRI (Fig. 48.10).

A number of techniques are available to evaluate the extent of white-matter involvement based on MRI intensity changes. Initial methods were semiquantitative, and involved the visual inspection of images. Changes could be compared among individuals, on a cross-sectional basis, or longitudinally in the same individual. Cross-sectional comparisons have been made by simply grouping the scans of patients and controls from 1 (least amount of white-matter changes) to 8 (greatest amount) (Masdeu et al., 1989). Most often used are scales describing the amount of white-matter changes. The Fazekas scale (Fazekas et al., 1987) has a range of 1–6. In the periventricular regions scores 0–3 can be given, and in the subcortical region scores 1–3 can be given for mild, moderate, or severe lesions, respectively. The Age-Related White-Matter Changes (ARWMC) scale (Wahlund et al., 2001) has a range from 0 to 30, where scores 0–3 can be given in five regions, each left and right. The Scheltens Rating Scale (Scheltens et al., 1993) ranges from 0 to 84 (scores 0–6 can be given in 13 subcortical regions and scores 0–2 for three periventricular regions). An example of a longitudinal scale is the Rotterdam Progression Scale (Prins et al., 2004) (range −7 to 7), which measures decrease, no change, or increase (−1, 0, 1, respectively) of white-matter changes for three periventricular regions and four subcortical regions.

These visual methods are giving way to semiautomatic (Gouw et al., 2008b) or even completely automatic methods, which use the matrix output from the MRI scanner to select voxels likely to correspond to abnormal white matter (Tiehuis et al., 2008). Ideally, images to be processed automatically should be obtained with good magnetic field homogeneity or with an additional sequence for inhomogeneity correction, small voxel size (1–2 mm3), and with three-dimensional acquisitions, where the entire brain is imaged with voxels having the same size in all three planes. In good-quality scans, automatic or semiautomatic segmentation methods can measure the extent of white-matter changes accurately and with a minimum of operator effort (de Boer et al., 2009). Not only the global amount of white-matter changes, but their location as well can be assessed automatically (van der Lijn et al., 2012).

Diffusion tensor imaging (DTI) has been extensively applied to the study of white-matter changes in older people (Jones et al., 1999; Vernooij et al., 2008; Barrick et al., 2010; Burzynska et al., 2010; Kim et al., 2011; Fu et al., 2012). DTI measurements indicating white-matter damage, particularly decreased functional anisotropy and increased radial diffusivity, have been found at autopsy to correlate with white-matter ischemic lesions, free-radical injury, and aberrant oligodendrocytes (Back et al., 2011). Not surprisingly, there is a better correlation between DTI measurements and those areas abnormal on FLAIR likely to be mildly to moderately affected, such as those located farther from the ventricles (Zhan et al., 2009). The correlation is lost in the periventricular region, with very high FLAIR values. DTI measurements of the corpus callosum have been used in the study of gait (Bhadelia et al., 2009). The corpus callosum affords an easy and appropriate target for DTI studies, because most fibers run parallel to each other and there is very little fiber crossing. In regions where major pathways cross perpendicularly, such as the superior longitudinal fasciculus and the corticospinal tract, axonal loss in one of the pathways may actually result in an increased anisotropy, as more of the remaining fibers are parallel to each other (Douaud et al., 2011). As regards gait, genu DTI abnormalities may simply reflect the involvement of frontal pathways by the disease process and the callosal fibers may have little or nothing to do with gait.

DTI findings in participants with a range of microvascular brain disease must be interpreted with caution, because hemodynamic changes, regardless of the integrity of white matter, can affect fractional anisotropy and other DTI parameters (Rudrapatna et al., 2012). While a number of controlled studies of elderly prone to falling have correlated impaired gait and balance with the presence of white-matter disease on CT or MRI (see, for instance, Masdeu et al., 1989; Srikanth et al., 2009), studies relating gait to DTI changes are scarce. In a study of 173 community-dwelling elderly, DTI measurements in the genu of the corpus callosum correlated with gait function measured by the Tinetti gait and balance scores (Bhadelia et al., 2009).

Disequilibrium may also be prominent in patients with hydrocephalus or with lesions in the medial aspect of the frontal lobe. However, those patients tend to have the gait disorder described below as “magnetic gait.”

Central disequilibrium is probably the commonest cause of the so-called “drop attacks,” sudden falls without warning or loss of consciousness in older individuals. Drop attacks were originally attributed to disease of the vertebrobasilar system, but this etiology of drop attacks in the elderly is probably not as common as subcortical hemispheric disease (Masdeu, 2004).