Gross Examination of the Brain and Spinal cord

Introduction Fixation and processing Brain weight and size Blood vessels External examination Cut Sections

Introduction and brain removal Head

General: Post mortem investigation is a fine art that should be approached with wisdom and keen observation. The following is only a guideline. Experience and imagination always help in solving difficult cases.

Safety: Universal precaution must be observed. Safety is the most important issue.

History: The first step of a thorough autopsy is to study the history and the medical record of the patients. In the context of neuropathology autopsy, special attention should be paid to symptoms, signs, and prior surgical history referring to the nervous system and its surrounding tissue. Particularly whent the patient has a history of muscular and peripheral nerve disease, an appropriate sample of peripheral nerve and muscle should be taken from the area where pathology is suspected.

Removal of the brain and spinal cord: The brain and spinal cord can be removed en bloc in both approaches. In general, the ventral approach is easier in adolescence and adults. The dorsal approach is easier in fetus, infants and children.

Ventral approach: The brain and the spinal cord can be removed by a ventral approach after the thoracic and abdominal organs are removed. This is perhaps the most commonly used method. This approach is also of particular value if pathology of the body of the spine.
Dorsal approach: The brain and spinal cord can also be removed by a dorsal approach. This approach is exceptionally valuable when pathologic changes and trauma to the neck and vertebral arteries are suspspected since these structures can be dissected and examined in great details in this approach; it is also useful in identifying spina bifida and in cases with meningocele, meningomyelocele and similar conditions. This approach also allows in situ recognition of tonsillar herniation.

Dislocation of the odontoid process: Put your finger in to the foramen magnum and rotate the head. If you can feel the odontoid process, it is dislocated.

Cervical spinal injury: run your fingers on the dorsal surface of the cervical-medullary junction and the cervical cord while the cord is still fresh. Softening can be felt when there is injury at the cervical-medullary junction. This method is not going to work in fixed bodies and also in cases with the brain and spinal cord removed from the dorsal approach (the atlas has been cut).

Cranial base fracture: The dura should be stripped off. The cranial vault and base should be shaken in frontal-occipital direction and then lateral direction to look for fracture line.

En bloc removal of the brain and spinal cord: The brain and spinal cord should be removed en bloc, preferred with neck dissection and dorsal approach, if the following conditions exist:

History of trauma to the neck (iatrogenic, intentional, and accidental) or shaken-impacted baby syndrome.
Sign of injury of the neck on external examination during autopsy.
The lesion is in this region (e.g., brainstem glioma, Chiari malformations)
The cause of death cannot be explained by the general autopsy, particularly with the history of a feverish illness.
Clinical history referring to abnormalities of cranial nerves.

CSF: A good volumne of CSF uncontaminated by blood can be taken from the interpeduncular cisterna by using a syringe and a needle. This procedure must be done before the spinal cord is dissected out otherwise the CSF would not be blood free. Attempts in removal of CSF from the ventricles are far less likely to be successful.

Surrounding tissue: The brain maintains an intimate and important relationship with the surround tissue, namely the dura and the cranial bone. This relationship can only be examined during the autopsy. When the body is returned for burial, it would be returned for good in most cases. It is of paramount important to examine the canial bone, the vertebral column and surrounding tissue during autopsy. When the patient has a history of the following conditions, a detailed examination of the cranial base and the vertebral column is always called.

Intracranial hemorrhage
Visual disturbance
Sellar mass
Aneurysm
Focal cranial nerve symptoms
Trauma and suspicion of child abuse
Cranial base tumor and bone tumor
Pathologic changes in the vertebral column.
History of severe infection of the head (such as sinusitis and dental abscess) or the spine.

The eye and optic nerve: Removal of the eyes and optic nerve is mandatory in cases of child abuse particulary in shaken baby syndrome. The eyes and optic tract should also be removed if there is suspected pathologic changes.

The middle ear: This is particularly important in children with meningitis as the middle ear can be a source of infection. The middle ear should be removed en block with the surrounding bone, fixed, decalcified, and the sliced and submitted for microscopic examination.

Carotid arteries: In case of stroke and particularly an embolic stroke is suspected clinically, the carotid arteries on both sides should be dissected and evaluated for atherosclerosis.

The vertebral arteries arise as the first part of the subclavian artery, transverse the foramen of the 6th cervical vertebra, and ascend through the transverse foramina of all higher cervical vertebrae. The artery pierces the atlanto-occipital membrane and the dura mater to enter the posterior cranial fossa through the foramen magnum.

Delicate portion: The segment of vertebral artery after the transverse foramen of the atlas and before entering the foramen of magnum do not have strong mechanical support and is very vulnerable to injury, in particular, twisting of the neck. A blow to the jaw resulting in a sudden twist of the head can injure this vessels and lead to sudden death. Injury of this segment of the vertebral artery will always result in blood accumlating in the cisterna magnum.

Blood in cisterna magnum: Blood in cisterna magnum is highly suggestive of of damage to the vertebral artery particularly if there is a history of trauma or a suspision of foul play. In forensic examination, a dissection of the vertebral column at the level of the foramen magnum is mandatory.

Fixation and processing Head

Culture: Appropriate cultures should be taken.

Frozen tissue: Frozen brain tissue, usually from the frontal lobe, should be stored fresh frozen if metabolic diseases are suspected.

For adequate fixation: 6 liters of formalin should be used per brain for optimal fixation. This is often difficult to perform because of its volume. The brain should at least be fixed in 2 liters of 20% formalin for two to, preferably, three weeks. For brains from adults and children older than one year, the brain can be kept from from distortion due to fixation by hanging the brain in formalin. The more common way is to hang it with a string passing through the basilar artery. Alternatively, the dura can also be used if it remains attached to the brain.

Alcohol hardening protocol for fetal and infantile brains (Modified from Rorke and Riggs, 1962): Fully fix the brain in 4% formaldehyde solution. Cut the brain into thick three or four slices. Transfer them to a mixture containing formalcohol (80% alcohol: 37% formaldehyde solution= 9:1) and let it fix for a week. Transfer the sections to 80% alcohol for 5 days and then to 95% alcohol. The condition of the tissue at this stage determines how long it is kept in the 95% alcohol.

Floating fetal and infantile brain: It is oftern impossible to hang a fetal or infantile brain in formalin. Fetal and infantile brains contains more water than adult brain and can therefore be floated in formalin in formalin more concentrated that 10%. This can be achieved by adding undiluted formalin to the formalin solution slowly until the brain float. This will avoid distortion due to fixation. As the brain is being fixed in the following two to three days, it will attain the same density as the formalin and sink. By then, the sunken brain will not distort further and it will not be necessary to add additional formalin.

Blood: Brains with hemorrhagic lesion will release a large amount of blood into the formalin. Brain are often not well fixed in bloody formalin. It is necessary to replace the bloody formalin with fresh 20% formalin on the second day after the autopsy.

Volume of blood loss: It is often difficult to estimate volume of the blood clot, the weight, however, is easy to get and would also accurately reflect the size of the hematoma.

Removing blood clots:

Fresh blood: If there is a ruptured aneurysm of the brain base accompanied by a lot of hemorrhage, the circle of Willis should be dissected out before fixation. Otherwise, the fixed blood clot will greatly hamper the dissection of the vascular structures that make the diagnosis of aneurysms difficult.
Fixed blood clots: In case if a brain with a ruptured aneurysm or AVM accompanied with a fixed blood clot is received, the blood cand be dissolved away by placing the fixed specimen in detergent solution for a few days.

Paraneoplastic disease: In addition to the brain and spinal cord, the following samples are needed,

Serum: Stored frozen.
CSF: Stored frozen.
Brain, spinal cord, and dorsal root ganglion: Frozen tissue should be procured from suspicious area and frozen in OCT for future frozen section.
Tumor under question: Frozen tissue in OCT.

Brain weight and size Head

Head circumference: The head circumference in infants and fetus should be measured. The biparietal diameter is more meanful if the fetus is under 22 weeks of gestation.

Accuracy: The use of brain weight as a reflection of brain volumn is accurate only if there is no severe edema, congestion, or loss of ventricular CSF during the weighing process. In severe brain edema, the brains have a strong tendency to bulge out; these brains often appear too big to fit into the cranial cavity. This phenomenon is particularly prominent in children and infants.

Sex: Male brain is about 10% heavier than female brain.

Brain weight is about 380 g at birth; 970 g at 1 year; 1120 g at 2 years; 1300 g at 5 years; 1400 g at 10 year; 1450 g at 19-21 year; 1430 g at 50 year; 1370 g at 60 year; 1330 g at 80 year. In females the maximum is 1340 g at age 18, which declines to 1140 g at 80.

During gestation, the brain weight to body weight ratio is about 1:7-8.

Cerebellum: In fully-grown human brain, the posterior tip of the cerebellum should parallel the occipital tip. In adult, the cerebellum represents about 12% of the total brain weight. In very young infants, the cerebellum represent only about 5-8% of the total brain weight. The posterior margin of the cerebellum typically falls short from the tip of the occipital lobe.

Blood vessels Head

Introduction: Blood vessels and dural sinuses must be examined in situ carefully if there is epidural and subdural hemorrhage. Hemorrhage into the interpeduncular cisterna (basically a form of subarachnoid hemorrhage) in an adult is very suggestive of a ruptured aneurysm. In premature newborns, hemorrhage in the interpeduncular cisterna and cisterna magna is often, but not always, resulted from extension of an intraventricular hemorrhage as a complication of prematurity.

Internal carotid artery:

The internal carotid artery is traditionally separated into 4 parts: the cervical part, the intrapetrosal part, intracavernous part, and the cerebral (supraclinoid) part. The later two are also known as the siphon of the internal artery.
For radiology interest: The internal carotid artery enters the dura around the level where the branch of the ophthalmic artery arise. Rupture of aneurysm below this level should not give rise to subarachnoid hemorrhage.
Anastomosis: The anastomosis of the internal carotid and external carotid artery through the opthalmic artery represent an important anastomotic pathway. If this anastomosis is normal, even complete occlusion to one of the four major blood supplies to the brain may not necessarily lead to insufficient regional blood flow of the brain.

Circle of Willis: A complete circle of Willis is found in only 25% of human subjects and does not but itself represents pathologic changes.

Atherosclerotic changes: They are common in the major arteries particularly the basilar artery and the circle of Willis. I have derived a grading system of atherosclerosis (Fung's classification):

Grade 0 (Normal): Vessels are semi-transparent, soft, thin, and collapsed. Blood can be seen through the blood vessels.
Grade 1: Vessels are less transparent, appears slightly opaque and thickened, but remain soft and not dilated. They do not collapse completely.
Grade 2: Vessels are ectactic, rigid, fibrotic and have a rigid lumen. No narrowing or obliteration is present.
Grade 3: Vessels are ectactic, fibrotic, and calcified. The wall is partially thickened and lumen is significantly narrowed or obliterated. The extent and location of obliteration should be documented.

Spinal infarction:

Spinal watershed areas: The upper thoracic (T1-T4) and first lumbar (L1) spinal segments are among the most vulnerable regions of the spinal cord for infarction. The intercostal arteries do not interconnect with other arteries in the same extensive fashion as the other extraspinal arteries in the cervical and lumbosarcral regions.
Dissecting aneurysm: Occlusion of one intercostal artery in a vulnerable region can result in a spinal cord infarction. This clinical picture is seen with dissecting aneurysms of the aorta or as a result of surgery on the aorta where more than one intercostal artery may be occluded.
Artery of Adamkiewiczi: this is a major arterial supply to the spinal cord and must be safed during kidney transplantation. Otherwise, the patient will develop spinal infarction.
The anterior portion of spinal cord at T4 and L1 level are also susceptible to vascular insult.

Blood in spinal subarachnoid space: A small amount of blood in the spinal subarachnoid space is a common feature in infants sustaining respiratory distress.

Batson’s plexus: The paravertebral venous plexus of Batson forms and extensive system of venous channels both within and alongside the spinal canal providing direct communication from peritoneal sites and the lower body to the cranial cavity. There are no valves in Batson’s plexus and flow may be bi-directional during the Valsalva manoeuvre or a change of body position. This plexus is also a favorable place for metastasis particularly mammary and prostatic carcinoma.

External examination Head

General:

The brain should be examined in a systemic manner. The first step is to look for missing structures. The brain is a symmetric structure and it is always helpful to compare one side with the other side; it is also important to examine the symmetry of both sides.
The size, location, macroscopic features of the lesions should be documented. Palpation of the brain is important because early infarction is more likely to appear as softening with minimal color changes. They are far more easily detectable by palpation than visual examination.

Herniations: The types include cingulate (falcine), uncal (hippocampal, transtentorial), tonsillar (cerebellar), upward herniation of the cerebellum, transclavarial (fracture) herniations.

Cingulate herniation:

Parasagittal infarction: Cingulate herniation can compromise the flow of the anterior cerebral artery and lead to parasagittal infarction.
Degree of aurosal is usually invertly proportional to the degree of deviation of the septum pellucidum and the aqueduct.

Uncal herniation:

Grooving of the parahippocampal gyrus. Lateral compression of the upper brain stem.
The posterior cerebral artery can be compressed by a herniated uncus easily. Compromised blood flow of the posterior cerebral artery may lead to infarct of in its territory that include the visual cortex. Blindness can be resulted. When it occur on one side, homonymous hemianopia will occor.
Kernohan's notch: notch on cerebral peduncle on the side contralateral the uncal herniation. Causes hemiparesis ipsilateral to the herniated side.
Diencenphalic downthrust: In the case of uncal (tentorial) herniation, this can be assessed by the noting the position of the mammary bodies in relation to a line joining the lateral angles of the inferior horns of the lateral ventricles (Greenhall line). Normally the mamillary bodies lie 1 or 2 mm above this line. A severe downthrus brings them 5 mm or more below it. [Oppenheimer pp.21]

Tonsillar herniation:

Herniation of the tonsillar will lead to compression of the brain stem.
In neonates, particularly premature infants, the herniated tonsil has a high tendency to undergo necrosis. It may be so severe that the herniated portion of the tonsil disappears and the subarachnoid space of the spinal cord is filled and expanded with necrotic cerebellar tissue. In less severe cases, microscopic fragments of cerebellar tissue can be found in the spinal subarachnoid space.

Upward herniation of the brain stem and cerebellum: this may be resulted from an increase in pressure in the brain stem (e.g. tumor), or a sudden decrease of pressure in the cerebellum (e.g. sudden withdrawal of fluid from the lateral ventricles). In this case, the upper surface of the celebellum will appear convex instead of the usual slightly concave.

Superior cerebellar artery: this artery may be compressed by the upward herniation upon the free edge of the tentorium and lead to infarction of the cerebellum.

Shape:

The shapen of infantile brain is overall more round than adult brains.
Patients with Down's syndrome may have a box shaped brain.
Childhood or infant brain with history of prematurity often has elongation along the anteroposterior axis.

Operculum: In mature full term infant, the operculum should be big enough to cover the insula completely.

Melanin pigment is not infrequently seen on the surface of the brain especially in black patients. The two most common sites are the inferior surface of the frontal tip and the anterior surface of the medulla.

Olfactory bulb and tract: It is sometime difficult to tell if the olfactory bulb is congenitally absent or not lost when the brain is removed. If the olfactory bulb is present, there will be a straight sulcus at the place of the olfactory tract. The olfactory bulb can be congenitally absent in only one side.

Fetal cortical convolution: The pattern of convolution in brains and the brain weigh of newborn may reflect the age of gestation more accurately than the body weight. That is, the body weight too high or too low for the gestational age but the brain weight corresponds more accurately for the gestational age.

Epidural hematoma usually produces more flattening of the gyrus than subdural hemorrhage.

Edema (including edema associated with meningitis) in an eldery patient with cortical hemorrhage can be missed easily because of the dilated ventricles.

Brownish discoloration of the cortex in elderly patients is due to lipofusin deposition.

In alcoholic patients, there may be multiple areas of hemosiderin staining on the brain surfaces indicating prior injuries to the brain due to falls.

Hemorrhage in the falx: Small intra-falcine hemorrhages are common in premature babies and usually do not carry serious clinical significance. They are particularly common in those with induction.

Pontomedullary Junction:

Forensic medicine: Hyperextension of the neck, frequently seen in shaking baby syndrome and neck injury in motor cycle accidents, the anterior surface of the pontomedullary junction may be coated with a very small amount of blood. Do not ignore these blood. Very frequently, there is a laceration separating the pons from the medulla and can be demonstrated easily by making a cut along the long axis of the brain stem along the mid-line.

Cut sections Head

Common artefacts: 'Swiss chess' artefact, toothpaste softening, pink haloes (a few mm in diameter, around small blood vessels).

Classical cutting sequence (coronal plane):

First make a coronal cut at the level of the mammary bodies to separate the brain into a frontal half and an occipital half. The slices the frontal half of the brain into 0.8 cm thick slabs on the coronal plan.
For the occipital half, examine the cerebral peduncles. Then remove the brainstem by making a cut at the horizontal level of the tips of the mammary bodies. Make sure that this cut is perpendicular to the long axis of the brainstem.
Slice the occipital half of the cerebrum in to 0.8 cm slabs.
Remove the brainstem from the cerebellum by cutting the cerebral peduncles. It is easier to approact it from the rostral end. Note: It is better to cut the cerebellum with the brainstem attached in horizontal plan if pathologic changes at the cerebellar peduncles and white matter diseases are suspicious.
Slice the brainstem into 0.3 cm horizontal slabs.
Slice the cerebellum into 0.3 cm sagittal slabs.

Premature fetus and neonates: Remove the brainstem by making a cut at the cerebral peduncles. Cut the cerebral hemispheres in coronal plane, the brainstem and cerebellum in horizontal plan.

Other plane: The brain can also be cut in horizontal and sagittal plane. These planes are often very useful for pathologic-radiographic correlation.

"Ribbon effect" or "reverse effect": first described by Larroche. This is not found in adults and is sometimes dramatic in neonatal hypoxic-ischemic injury. This refers to a diffuse reddish-brown color of the white matter while the neocrotic cortex is unusually white. Simply, the adult pattern of darker cortex and lighter white matter is "reversed" in these cases.

The substantia nigra starts to develop pigment at round 3-5 years old and is completely pigmented at about 18 years old.

Hydrocephalus: The anterior tip of the lateral ventricle should not protrude farther than the tip of the temporal tip. Otherwise, hydrocephalus should be suspected.

The thickness of the cortical ribbon is about 0.25 to 0.5 cm. The general trend is that the primary sensory cortex such as the visual cortex is the thinnest. The motor cortex is the thickest. The association cortex is in between.

Pontine tegmentum: The thickness of the pontine tegmentum of the pons should be about half as thick as the basis pontis.

Septum pellucidum is frequently disrupted in fetus with hydrocephalus.

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