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Purpose For stereotactic radiation therapy of intracranial malignancies, a patient’s head needs to be immobilized with high accuracy. Fixation devices such as invasive stereotactic head frames or non-invasive thermoplastic mask systems are often used. However, especially stereotactic high-precision masks often cause discomfort for patients due to a long manufacturing time during which the patient is required to lie still and because the face is covered, including the mouth, nose, eyes, and ears. To avoid these issues, the target was to develop a non-invasive 3D-printable mask system with at least the accuracy of the high-precision masks, for producing masks which can be manufactured in the absence of patients and which allow the eyes, mouth, and nose to be uncovered during therapy. Methods For four volunteers, a personalized 3D-printed mask based on magnetic resonance imaging (MRI) data was designed and manufactured using fused filament fabrication (FFF). Additionally, for each of the volunteers, a conventional thermoplastic stereotactic high-precision mask from Brainlab AG (Munich, Germany) was fabricated. The intra-fractional fixation accuracy for each mask and volunteer was evaluated using the motion-correction algorithm of functional MRI measurements with and without guided motion. Results The average values for the translations and rotations of the volunteers’ heads lie in the range between ±1 mm and ±1° for both masks. Interestingly, the standard deviations and the relative and absolute 3D displacements are lower for the 3D-printed masks compared to the Brainlab masks. Conclusion It could be shown that the intra-fractional fixation accuracy of the 3D-printed masks was higher than for the conventional stereotactic high-precision masks.

The arterial supply of the brain is provided by the carotid system (anterior circulation) and the vertebro-basilar system (posterior circulation). The arteries with their branches and the vascular territories they supply are described. Clinical syndromes resulting from pathology of the respective artery and involved structures are tabulated and include anterior cerebral artery syndrome, middle cerebral artery syndrome, anterior inferior cerebellar artery syndrome (AICA syndrome or lateral pontine syndrome), posterior inferior cerebellar artery syndrome (PICA syndrome), and posterior cerebral artery syndrome.

Gliosarcoma (WHO grade IV) is a variant of IDH-wild-type glioblastoma, characterized by a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation.

Progressive supranuclear palsy (PSP) and cortico-basal degeneration (CBD) are thought to represent a disease spectrum. The clinical presentation depends on the localization and distribution of the pathological lesions, i.e., PSP affects the hindbrain structures, whereas CBD affects the forebrain.

The light-microscopical buildup of the various parts of the nervous system is described. The cerebral cortex contains pyramidal cells, spiny non-pyramidal cells and aspiny non-pyramidal cells, stellate or granule cells, fusiform cells, horizontal cells of Cajal, and cells of Martinotti. The parcellation of the cerebral cortex defined as architectonics is based on cytoarchitectonics, myeloarchitectonics, pigmentarchitectonics, angioarchitectonics, chemoarchitectonics, dendrite architectonics, glia architectonics, receptor architectonics, and in vivo architectonics. The layering of the cortex is described. The concepts of minicolumns, granular cortex, agranular cortex, supragranular layers (I, II, and III), infragranular layers (V and VI), heterotypic cortex, and homotypic cortex are presented. Various features of interneurons are described. The hippocampus is a bilaminar structure made up of the cornu ammonis (hippocampus proper) and the dentate gyrus (fascia dentata). Their strata, i.e., alveus, stratum oriens, stratum pyramidale with CA1, CA2, CA3, CA4, stratum radiatum, stratum lacunosum, and stratum moleculare of the cornu ammonis and the stratum moleculare, stratum granulosum, and polymorphic layer of the dentate gyrus are characterized. The following description includes the entorhinal cortex, nucleus basalis Meynert, amygdala, white matter, basal ganglia (i.e., caudate nucleus and putamen, globus pallidus), nucleus accumbens, diencephalon with thalamus made up of various nuclear groups, hypothalamus, the medial hypothalamic region, mesencephalon with the substantia nigra and nucleus ruber, pons with the locus coeruleus, medulla oblongata with the area postrema, pyramis, and inferior olivary complex. The cerebellum is composed of the cerebellar cortex (with granular cells, Golgi cells, Purkinje cells, basket cells, and stellate cells), cerebellar white matter, and cerebellar nuclei embedded in the white matter (dentate nucleus, emboliform nucleus, and fusiform nucleus). The spinal cord is made up of gray matter (dorsal horn, ventral horn, and lateral horn) surrounded by white matter. Ventricles are lined by a single layer of cuboidal ependymal cells with numerous microvilli on the ventricular side. The choroid plexus is a villous structure made up of a single layer of cuboidal epithelium which rests on a basal lamina.

Choroid plexus tumors are intraventricular; papillary neoplasms are derived from choroid plexus epithelium: choroid plexus papilloma (WHO grade I), atypical choroid plexus papilloma (WHO grade II), and choroid plexus carcinoma (WHO grade III).

Therapy-associated neuropathologic changes include radiation necrosis and fibrosis, therapy-induced leukoencephalopathies, vasculopathies, and secondary neoplasms.

Tumors affecting the sellar region include pituitary adenoma, pituitary carcinoma as well as craniopharyngioma, other tumors (e.g., gangliocytoma, spindle cell oncocytoma of the adenohypophysis, pituicytomas), and cystic lesions.

Fronto-temporal dementia (FTD) or fronto-temporal lobar dementia (FTLD) includes four clinical subgroups, i.e., semantic dementia, progressive non-fluent aphasia, FTD-behavioral variant, and FTD with motor neuron disease/ALS.

Localization of brain function is the goal of cognitive neuroscience, behavioral neurology, and clinical neuroanatomy. Its armamentarium relies on connectional methods (diffusion tensor imaging), correlational methods (e.g., magnetic resonance imaging, functional magnetic resonance imaging, voxel-based morphometry, positron emission tomography), lesion models (e.g., traumatic brain injuries), and stimulation methods (e.g., transcranial magnetic stimulation). Theories of brain function include holistic, localizationist, and associationist models.

Demyelination is characterized by destruction of normal myelin with an elative preservation of axons. Demyelinating diseases encompass among others multiple sclerosis (MS), neuromyelitis optica (Devic disease), acute disseminated encephalomyelitis (ADEM), and acute hemorrhagic leukoencephalopathy (AHL).

Anaplastic astrocytoma (AA) is a diffusely infiltrating astrocytoma with focal or dispersed anaplasia, significant proliferative activity, and a mutation in either the IDH1 or IDH2 gene.

Temporal lobe epilepsy (also called mesial temporal lobe epilepsy), the most frequent form of partial epilepsy in adults, is clinically characterized by alterations in consciousness combined by various functional manifestations including sensory, motor, psychic, and autonomic.

Multiple system atrophy (MSA) is a rare disorder including, based on clinical presentation, a predominantly parkinsonism subtype (MSA-P) (80% of cases) and a predominantly cerebellar subtype (MSA-C).

The nervous system is subdivided into the central nervous system (CNS) and the peripheral nervous system (PNS). Incoming stimuli are processed at different levels including unconditioned reflex, conditioned reflex, instrumental reaction, and cognitive processes. Based on functional aspects, the nervous system can also be subdivided into the cerebrospinal nervous system and the autonomic nervous system. The concepts of the organization of cortical areas following a somatotopic organization, primary cortical areas, and secondary cortical areas are briefly given. Definitions of gray and white matter, nuclei, ganglia, tracts, and neuropil are provided.

Alzheimer’s disease (AD) is the most frequent neurodegenerative disease. It is clinically characterized by progressive dementia with increasing loss of memory, intellectual dysfunction, disturbances in speech, apraxia, agnosia, agitation, and restlessness. Early-onset AD (before age 65) versus late-onset AD might be distinguished.

The venous blood is collected by the veins, drained into the dural sinuses and emptied into the jugular vein by emissary veins, cerebral veins, dural sinuses, internal jugular vein, and brachicephalic vein. The cerebral venous system is made up of superficial (cortical) cerebral veins and deep (subependymal) cerebral veins. A list of veins with their anatomical specifics, the drained territory and their draining is provided. The draining system of the unpaired and paired dural venous sinuses is described.

The ventricular system (i.e., lateral ventricles, third ventricle, and fourth ventricle) is composed of hollow cavities which are located in the telencephalon, diencephalon, and mesencephalon and extend via the pons to the medulla. They harbor the cerebrospinal fluid (CSF) which is produced by the choroid plexuses and fulfills nutritive and protective functions of the brain. The exchange of chemical substances between the arterial blood, the CSF and the brain is regulated by the barrier system which is made up of the blood–brain barrier (BBB), the brain–liquor barrier (BLB), and the blood–liquor barrier.

Meningiomas are usually benign tumors arising from meningeal or arachnoithelial cells. They occur frequently and make up 40–45% of tumors seen in the daily clinical practice. According to biologic behavior, meningioma (with various histologic subtypes) (WHO grade I), atypical meningioma (WHO grade II), and anaplastic meningioma (WHO grade III) are distinguished.

Brain edema or brain swelling is defined as an increase in brain volume due to a localized or diffuse abnormal accumulation of water and sodium within the brain parenchyma. Vasogenic edema, cytotoxic edema, hydrocephalic or interstitial edema, and osmotic edema are distinguished based on pathogenetic mechanisms. Edema manifests as a general or focal brain swelling with consecutive effacement of sulci and compression of ventricles and/or basal cisterns.

“Epilepsy” is not a single disease entity. Epilepsies are many syndromes and diseases that have a multitude of different manifestations and causes. Definition of specific events is of eminent importance which include among others epileptic seizure, epilepsy, ictus and ictal event, postictal period, postictal phenomena, interictal period, seizure focus, epileptogenicity, epileptic spike focus, epileptogenic lesion, and epileptogenic zone or region.

Oligodendroglioma (WHO grade II) is a diffusely infiltrating, slow-growing glioma with IDH1 or IDH2 mutation and co-deletion of chromosomal arms 1p and 19q. It affects adults (mean age: 40–45 years) and involves the cortex and white matter of the cerebral hemispheres (frontal lobe in 50–65% of all cases).

Vascular dementia (VaD) is defined as a neurocognitive disorder, which is explained by numerous vascular causes in the general absence of other pathologies. It includes multi-infarct dementia, small vessel disease (SVD), strategic infarct dementia, hypoperfusion dementia, hemorrhagic dementia, and mixed dementia.

A stroke is clinically characterized by an abrupt onset of focal neurological signs lasting more than 24 h while in transient ischemic attack (TIA) the focal signs last less than 24 h. Two types of stroke are distinguished: ischemic stroke (due to an occlusion of a blood vessel with focal tissue ischemia and infarction), and hemorrhagic stroke (due to a rupture of a blood vessel with extravasation of blood and subsequent tissue damage). Clinical signs depend on the anatomical region involved.

The therapeutic response can be defined as complete remission/response (CR), partial remission/response (PR), stable disease, or progressive disease.

Neuropathology is the medical discipline concerned with the study of diseases affecting the central and peripheral nervous system as well as muscle. Its aim is to describe the structural, biochemical, molecular, and functional changes in the various cells which make up the nervous system. Using morphologic, immunologic, and molecular biological techniques, neuropathology tries to explain the signs and symptoms of patients. Delivering a clear-cut diagnosis provides the rational basis for patient care and therapy. Specimens for analysis are obtained through autopsy (brain, spinal cord, meninges), open brain surgery, biopsy (stereotactic or navigated biopsy, muscle and nerve biopsy), and lumbar puncture. The procedures for removal, fixation, and cutting of the brain and spinal cord, fixation and processing of tissue are crucial in the analysis pipeline. Staining techniques for tissue received in the neuropathology laboratory include classical stains (Hematoxylin and Eosin (H&E)), special stains (Periodic acid-Schiff (PAS)), diastase-sensitive PAS or PAS with diastase digestion, Alcian blue), and special stains for connective tissue. Special neuro-stains include cresyl violet (Nissl stain), Luxol fast blue (LFB), phosphotungstic acid hematoxylin (PTAH), modified Bielschowsky, and Gallyas stain. The principles of immunohistochemistry are described and supplemented by short characterization of markers for neurons, synapses, astroglia, oligodendroglia, myelin, microglia, neurodegeneration, tumors, vessels, hematopoietic and lymphatic cells, proliferation markers in tumors, and markers for infectious agents. Immunohistochemical panels for the diagnostic setting are provided. Other techniques used in neuropathology comprise electron microscopy, fluorescence microscopy, enzyme histochemistry, and in situ hybridization (ISH). Molecular biology techniques as used in neuropathology include blot techniques (Western blot to visualize proteins, Northern blot to visualize RNA, Southern blot to visualize DNA, Dot blot), molecular imaging with imaging a mutation after sequencing and imaging a deletion, duplication with RT-PCR as well as microarray techniques. Other imaging techniques, developed during the last decades, include Confocal Laser Scanning Microscopy, Multiphoton Confocal Fluorescence Microscopy, Atomic Force Microscopy (AFM), and many others.

Pituitary adenoma is a neoplastic proliferation of anterior pituitary hormone-producing cells. The tumors are typically benign, but can be aggressive and invasive into adjacent structures. Based on its hormonal activity, pituitary adenoma is characterized as somatotroph, lactotroph, thyrotroph, corticotroph, gonadotroph adenoma, null cell, plurihormonal, and double adenoma. In addition, atypical pituitary adenoma, pituitary carcinoma, pituitary blastoma, and pituitary hyperplasia are considered.

The histological constituents of the nervous system include neurons which can be classified based (a) on the number of cell processes as unipolar, bipolar, pseudounipolar neuron, and multipolar, (b) types of neuronal connections as projection neurons or interneurons. The synapse, composed of the presynaptic membrane, synaptic cleft, and postsynaptic membrane, can be excitatory or inhibitory. The classification of synapses (asymmetric, symmetric, axo-dendritic, axo-somatic, axo-axonal) was widened by considering the tripartite synapse and the tetrapartite synapse or “synaptic quadriga.” Many genes are involved in the regulation of synaptic proteins dealing with presynaptic neurotransmitter release, postsynaptic proteins, and trans-synaptic communication. A description of nerve fibers and peripheral nerve is provided.

Desmoplastic astrocytoma/ganglioglioma (DIA/DIG) is a benign glioneuronal tumor composed of a prominent desmoplastic stroma with a neuroepithelial population restricted either to neoplastic astrocytes—desmoplastic infantile astrocytoma (DIA)—or to astrocytes together with a variable mature neuronal component—desmoplastic infantile ganglioglioma (DIG)—sometimes with aggregates of poorly differentiated cells. This rare tumor affects young patients (infants: 1–24 months; non-infantile cases: 5–25 years).

Pilocytic astrocytoma (PA) is an astrocytoma classically characterized by a biphasic pattern with variable proportions of compacted bipolar cells with Rosenthal fibers and loose-textured multipolar cells with microcysts and occasional granular bodies. Children are affected during the first two decades of life.

Malformations of intracranial vessels include arteriovenous malformation, cavernous hemangioma, capillary telangiectasis, capillary hemangioma, venous angioma, and varix of the vein of Galen.

The classification of embryonal tumors still remains in flow and will change based on the acquisition of new molecular insight. Currently, major tumor categories include medulloblastoma, embryonal tumor with multilayered rosettes (ETMR), C19MC-altered, embryonal tumor with multilayered rosettes, NOS (not otherwise specified), other CNS embryonal tumors (medulloepithelioma, CNS neuroblastoma, CNS ganglioneuroblastoma, CNS embryonal tumor (NOS)), atypical teratoid/rhabdoid tumor (AT/RT), and CNS embryonal tumor with rhabdoid features.

Acute demyelinating encephalomyelitis (ADEM) is clinically characterized by fever, headache, impaired conscious level, meningism, seizures, and progressive neurological signs.

Tumors affecting the peripheral nervous system include schwannoma, neurofibroma, perineurioma, malignant peripheral nerve sheath tumor (MPNST), neurofibromatosis type I, neurofibromatosis type II, and schwannomatosis.

Lewy body disease (LBD) is a chronic progressive neuropsychiatric disorder characterized by parkinsonism with or without dementia. Dementia might be the predominant symptom while parkinsonian symptoms occur later during the course of the disease. Several types of LBD are distinguished, i.e., brain stem type (= Parkinson’s disease), traditional type, diffuse type = diffuse Lewy body disease (frequent form and rare form), and cerebral type. Staging of the lesions and regions involves results in four stages.

Pineocytoma (WHO grade I), pineal parenchymal tumor of intermediate differentiation (WHO grades II and III), pineoblastoma (WHO grade IV), and papillary tumor of the pineal region are tumors affecting the pineal region. These tumors are rare and can affect persons of all ages.

Germ cell tumors affecting the nervous system include germinoma, yolk sac tumor, embryonal carcinoma, choriocarcinoma, teratoma, and mixed germ cell tumors.