1.3 Central & Autonomic Nervous System Physiology & Neurological Disorders

1.3 Central & Autonomic Nervous System Physiology & Neurological Disorders

Safe neuroanesthesia and perioperative neurologic care depend on preserving cerebral perfusion pressure, controlling intracranial dynamics, and managing autonomic and neuromuscular junction pathologies.

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1. Cerebral Blood Flow (CBF) & Autoregulation

• Normal Global CBF: $50 \text{ mL}/100\text{g}/\text{min}$ (approximately $750 \text{ mL/min}$, or $15\%$ of total resting cardiac output).
  • Cortical Gray Matter: $\approx 80 \text{ mL}/100\text{g}/\text{min}$
  • Subcortical White Matter: $\approx 20 \text{ mL}/100\text{g}/\text{min}$
• Cerebral Metabolic Rate for Oxygen ($CMRO_2$): $3.0 - 3.5 \text{ mL } O_2/100\text{g}/\text{min}$ (accounts for $\approx 20\%$ of total body resting oxygen consumption).

+-------------------------------------------------------------------------+
|                   CEREBRAL BLOOD FLOW AUTOREGULATION                    |
+-------------------------------------------------------------------------+
|                                                                         |
|   CBF (mL/100g/min)                                                     |
|    100 |                  +-----------------------+ (Hyperperfusion)    |
|        |                 /                         \                    |
|     50 |----------------+   AUTOREGULATION PLATEAU  +-----------------  |
|        |               /      (50 - 150 mmHg MAP)    \                  |
|      0 +--------------+-------------------------------+--------->      |
|       0              50                              150       200      |
|                               MAP (mmHg)                                |
+-------------------------------------------------------------------------+

Autoregulation Dynamics

• Autoregulation Range: In normotensive adults, CBF is maintained constant across Mean Arterial Pressures of $50 - 150 \text{ mmHg}$ (or CPP $50 - 150 \text{ mmHg}$).
• Rightward Curve Shift in Chronic Hypertension: Long-standing hypertension causes arteriolar hypertrophy, shifting the autoregulation curve to the right (e.g., $80 - 180 \text{ mmHg}$). Lowering blood pressure into a "normal" range ($MAP \approx 65 \text{ mmHg}$) can precipitate cerebral hypoperfusion and ischemic stroke in these patients.

Determinants & Modulators of CBF

1. $PaCO_2$ Responsiveness: Between $PaCO_2$ of $20 - 80 \text{ mmHg}$, CBF changes in a linear fashion by $1 - 2 \text{ mL}/100\text{g}/\text{min}$ per $1 \text{ mmHg}$ change in $PaCO_2$ (or $\approx 2 - 4\%$ change in CBF per mmHg).
   • Hyperventilation ($PaCO_2 \; 30 - 35 \text{ mmHg}$): Rapidly lowers ICP via cerebral vasoconstriction. Effects diminish after $12 - 24 \text{ hours}$ due to renal/CSF bicarbonate buffering. Excessive hyperventilation ($PaCO_2 < 25 \text{ mmHg}$) induces severe cerebral ischemia.
2. $PaO_2$ Responsiveness: CBF does not significantly change until $PaO_2$ falls below $50 - 60 \text{ mmHg}$, at which point profound arterial vasodilation occurs to prevent tissue hypoxia.
3. Temperature: CBF and $CMRO_2$ decrease by $6 - 7\%$ for every $1^\circ\text{C}$ decrease in brain temperature. At temperatures below $20^\circ\text{C}$, the electroencephalogram (EEG) becomes isoelectric.
4. Anesthetic Agent Effects (Coupling vs. Uncoupling):
   • IV Anesthetics (Propofol, Etomidate, Barbiturates): Produce coupled reductions in both $CMRO_2$ and CBF, decreasing intracranial blood volume and lowering ICP. (Ketamine is an exception: increases CBF and $CMRO_2$).
   • Volatile Anesthetics (Isoflurane, Sevoflurane, Desflurane): Cause intrinsic dose-dependent cerebral vasodilation while decreasing $CMRO_2$. At concentrations $>1.0 \text{ MAC}$, intrinsic vasodilation overcomes metabolic depression (uncoupling), leading to increased CBF and ICP.

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2. Intracranial Dynamics & The Monro-Kellie Doctrine

+-------------------------------------------------------------------------+
|                        MONRO-KELLIE HYPOTHESIS                          |
+-------------------------------------------------------------------------+
|  Rigid Skull Vault = Brain Tissue (80%) + Blood (10%) + CSF (10%)       |
|                                                                         |
|  An increase in the volume of one cranial component must be offset     |
|  by a compensatory decrease in another, or ICP will exponentially rise. |
+-------------------------------------------------------------------------+

• Normal Intracranial Pressure (ICP): $5 - 15 \text{ mmHg}$. Intracranial hypertension is defined as sustained ICP $>20 \text{ mmHg}$.
• Cerebral Perfusion Pressure (CPP):

$$CPP = MAP - ICP \quad (\text{or } MAP - CVP, \text{ whichever is higher})$$

• Target CPP in Neurological Injury: $60 - 70 \text{ mmHg}$ (avoid $<50 \text{ mmHg}$ to prevent ischemia; avoid $>70 \text{ mmHg}$ to prevent vasogenic edema and ARDS).

Cushing's Triad

A late, life-threatening manifestation of severely elevated ICP and impending transtentorial herniation:

1. Hypertension (with widened pulse pressure)
2. Bradycardia (reflex vagal response to severe systemic hypertension)
3. Irregular Respirations / Respiratory Depression (brainstem compression)

Cerebrospinal Fluid (CSF) Kinetics

• Production: Formed by ependymal cells of the choroid plexus at a rate of $0.35 - 0.40 \text{ mL/min}$ ($\approx 500 \text{ mL/day}$). Total adult CSF volume is $\approx 150 \text{ mL}$.
• Flow & Absorption: Lateral ventricles $\to$ Foramen of Monro $\to$ 3rd Ventricle $\to$ Cerebral Aqueduct of Sylvius $\to$ 4th Ventricle $\to$ Foramina of Luschka & Magendie $\to$ Subarachnoid space $\to$ Absorbed via arachnoid villi/granulations into the superior sagittal sinus.

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3. Autonomic Nervous System Receptors & Second Messengers

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4. Autonomic Dysreflexia (Hyperreflexia)

• Etiology: Occurs in patients with spinal cord transection at or above the T6 level (rare below T10) after the acute spinal shock phase has resolved (typically weeks to months post-injury; incidence $\approx 85\%$ in lesions above T6).
• Pathophysiologic Cascade:
  1. Cutaneous or visceral noxious stimulation below the cord lesion (most commonly bladder distension $\approx 85\%$, bowel impaction, surgical manipulation, uterine contractions).
  2. Triggers massive, uninhibited sympathetic discharge from the isolated isolated spinal cord below the level of injury.
  3. Intense splanchnic and peripheral arteriolar vasoconstriction produces severe, paroxysmal systemic hypertension.
  4. Carotid and aortic baroreceptors detect severe hypertension, triggering compensatory vagal efferent discharge $\to$ bradycardia and cutaneous vasodilation above the level of the lesion (flushing, diaphoresis, headache, nasal congestion).
  5. Central descending inhibitory impulses are blocked from traversing the injured spinal cord, perpetuating vasoconstriction below T6.
• Complications: Intracranial hemorrhage, encephalopathy, seizures, acute pulmonary edema, lethal ventricular arrhythmias.
• Anesthetic Management:
  • General anesthesia or deep spinal anesthesia (which effectively blocks the afferent sensory limb) prevents autonomic hyperreflexia during surgery even in patients with complete sensory loss.
  • First-line emergency treatment: Remove noxious stimulus, deepen anesthetic depth, and administer rapidly acting vasodilators (sodium nitroprusside, nitroglycerin, nicardipine).

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5. Neuromuscular Junction Pathology: Myasthenia Gravis vs. Lambert-Eaton

+------------------------------------+-------------------------------------+
|      MYASTHENIA GRAVIS (MG)        |  LAMBERT-EATON SYNDROME (LEMS)      |
+------------------------------------+-------------------------------------+
| Postsynaptic AChR Autoantibodies   | Presynaptic P/Q-Type VGCC Antibodies|
| Weakness WORSENS with exertion     | Weakness IMPROVES with exercise     |
| Associated with Thymoma (75%)      | Associated with SCLC (>60%)         |
| Resistant to Succinylcholine       | SENSITIVE to Succinylcholine        |
| Exquisitely SENSITIVE to NDNMBAs   | Exquisitely SENSITIVE to NDNMBAs    |
+------------------------------------+-------------------------------------+